The present investigation aimed at identifying differences in muscle structural composition, substrate selection, and performance capacity in highly trained endurance athletes as a consequence of ...consuming a high-fat or a low-fat diet.
Eleven duathletes ingested high-fat (53% fat; HF) or high-carbohydrate diets (17% fat; LF) for 5 wk in a randomized crossover design.
In m. vastus lateralis, oxidative capacity estimated as volume of mitochondria per volume of muscle fiber (HF: 9.86 +/- 0.36 vs LF: 9.79 +/- 0.52%, mean +/- SE) was not different after the two diet periods. Intramyocellular lipid (IMCL) was significantly increased after HF compared with LF (1.54 +/- 0.27% vs 0.69 +/- 0.09%, P = 0.0076). Glycogen content was lower after HF than after LF, but this difference was not statistically significant (487.8 +/- 38.2 vs 534.4 +/- 32.6 mmol x kg-1 dry weight, P = 0.2454). Maximal power and OV0312O(2max) (63.6 +/- 0.9 vs 63.9 +/- 1.2 mL O(2) x min-1 x kg-1 on HF and LF) during an incremental exercise test to exhaustion were not different between the two diet periods. Total work output during a 20-min all-out time trial (298 +/- 6 vs 297 +/- 7 W) on a bicycle ergometer as well as half-marathon running time (80 min 12 s +/- 86 s vs 80 min 24 s +/- 82 s) were not different between HF and LF. Blood lactate concentrations and respiratory exchange ratios (RER) were significantly lower after HF than after LF at rest and during all submaximal exercise loads.
Muscle glycogen stores were maintained after a 5-wk high-fat diet period whereas IMCL content was more than doubled. Endurance performance capacity was maintained at moderate to high-exercise intensities with a significantly larger contribution of lipids to total energy turnover.
1 Service de Physiologie Clinique et des Explorations Fonctionnelles Respiratoires et de l'Exercice, Département de Physiologie, Équipe d'Accueil 3072, Strasbourg, France; 2 Institute of Anatomy, ...University of Bern, Bern, Switzerland; 3 Service de Cardiologie, Hôpitaux Civils de Colmar, Colmar, France; and 4 U-446 Institut National de la Santé et de la Recherche Médicale, Faculté de Pharmacie, Châtenay-Malabry, France
Submitted 29 March 2005
; accepted in final form 1 December 2005
This study investigates whether adaptations of mitochondrial function accompany the improvement of endurance performance capacity observed in well-trained athletes after an intermittent hypoxic training program. Fifteen endurance-trained athletes performed two weekly training sessions on treadmill at the velocity associated with the second ventilatory threshold (VT 2 ) with inspired O 2 fraction = 14.5% hypoxic group (Hyp), n = 8 or with inspired O 2 fraction = 21% normoxic group (Nor), n = 7, integrated into their usual training, for 6 wk. Before and after training, oxygen uptake ( O 2 ) and speed at VT 2 , maximal O 2 ( O 2 max ), and time to exhaustion at velocity of O 2 max (minimal speed associated with O 2 max ) were measured, and muscle biopsies of vastus lateralis were harvested. Muscle oxidative capacities and sensitivity of mitochondrial respiration to ADP ( K m ) were evaluated on permeabilized muscle fibers. Time to exhaustion, O 2 at VT 2 , and O 2 max were significantly improved in Hyp (+42, +8, and +5%, respectively) but not in Nor. No increase in muscle oxidative capacity was obtained with either training protocol. However, mitochondrial regulation shifted to a more oxidative profile in Hyp only as shown by the increased K m for ADP (Nor: before 476 ± 63, after 524 ± 62 µM, not significant; Hyp: before 441 ± 59, after 694 ± 51 µM, P < 0.05). Thus including hypoxia sessions into the usual training of athletes qualitatively ameliorates mitochondrial function by increasing the respiratory control by creatine, providing a tighter integration between ATP demand and supply.
intermittent hypoxia training; skeletal muscle; mitochondria; time to exhaustion; endurance athletes
Address for reprint requests and other correspondence: R. Richard, Hôpital Civil-Service des Explorations Fonctionnelles Respiratoires et de l'Exercice, 1 place de l'Hôpital, BP 426, 67091 Strasbourg Cedex, France (e-mail: Ruddy.Richard{at}physio-ulp.u-strasbg.fr )
With lengthening (eccentric) muscle contractions, the magnitude of locomotor-muscle mass and strength increase has been demonstrated to be greater compared with shortening (concentric) muscle ...contractions. In healthy subjects, energy demand and heart rate responses with eccentric exercise are small relative to the amount of muscle force produced. Thus, eccentric exercise may be an attractive alternative to resistance exercise for patients with limited cardiovascular exercise tolerance.
We tested the cardiovascular tolerance of eccentric exercise in 13 coronary patients (ages 40-66) with preserved and/or mild reduced left ventricular function. Patients were randomly assigned to either an eccentric (ECC; N = 7) or a concentric (CON; N = 6) training group and trained for 8 wk. Training workload was increased progressively (from week 1 to 5) to an intensity equivalent to 60% OV0312O(2peak).
On average, maximum power output achieved with ECC was fourfold compared with CON (357 +/- 96 W vs 97 +/- 21 W; P < 0.005), whereas measures of oxygen uptake and blood lactate were significantly lower (P < 0.05 each), and ratings of perceived exertion were similar for ECC and CON. During a 20-min session of ECC and CON, central hemodynamics was measured by means of right heart catheterization. During ECC, responses of mean arterial blood pressure, systemic vascular resistance, pulmonary capillary pressure, cardiac index, and stroke work of the left ventricle on average were in the normal range of values and similar to those observed during CON. Compared with baseline, after 8 wk of training, echocardiographic left ventricular function was unchanged.
The results indicate uncoupling of skeletal muscle load and cardiovascular stress during ECC. For low-risk patients with coronary heart disease without angina, inducible ischemia, or left ventricular dysfunction, ECC can be recommended as a safe new approach to perform high-load muscular exercise training with minimal cardiovascular stress.
We hypothesized that in untrained individuals (n=6) a single bout of ergometer endurance exercise provokes a concerted response of muscle transcripts towards a slow-oxidative muscle phenotype over a ...24-h period. We further hypothesized this response during recovery to be attenuated after six weeks of endurance training. We monitored the expression profile of 220 selected transcripts in muscle biopsies before as well as 1, 8, and 24 h after a 30-min near-maximal bout of exercise. The generalized gene response of untrained vastus lateralis muscle peaked after 8 h of recovery (P=0.001). It involved multiple transcripts of oxidative metabolism and glycolysis. Angiogenic and cell regulatory transcripts were transiently reduced after 1 h independent of the training state. In the trained state, the induction of most transcripts 8 h after exercise was less pronounced despite a moderately higher relative exercise intensity, partially because of increased steady-state mRNA concentration, and the level of metabolic and extracellular RNAs was reduced during recovery from exercise. Our data suggest that the general response of the transcriptome for regulatory and metabolic processes is different in the trained state. Thus, the response is specifically modified with repeated bouts of endurance exercise during which muscle adjustments are established.
1 Department of Anatomy, University of Berne, Berne, Switzerland, and 2 Unité Mixte de Recherche 5123, Centre National de la Recherche Scientifique, Université Lyon 1, Lyon, France
Submitted 10 ...February 2004
; accepted in final form 4 March 2005
The hypothesis was tested that differential, coregulated transcriptional adaptations of various cellular pathways would occur early with increased mechanical loading of atrophied skeletal muscle and relate to concurrent damage of muscle fibers. Atrophy and slow-to-fast fiber transformation of rat soleus muscle was provoked by 14 days of hindlimb suspension (HS). Subsequent reloading of hindlimbs caused a fourfold increase in the percentage of muscle fibers, demonstrating endomysial tenascin-C staining. Five days after reloading, when 10% of the fibers were damaged, the normal muscle weight and slow-type fiber percentage were reestablished. Microarray analysis revealed major, biphasic patterns of gene expressional alterations with reloading that distinguish between treatments and gene ontologies. Transcript levels of factors involved in protein synthesis and certain proteasomal mRNAs were increased after 1 day of reloading and correlated to the percentage of fibers surrounded by tenascin-C. By contrast, levels of gene messages for fatty acid transporters, respiratory chain constituents, and voltage-gated cation channels were transiently reduced after 1 day of muscle loading and associated with the number of damaged fibers and the regain in muscle weight. This coregulation points toward important retooling of oxidative metabolism and the T- and SR-tubular systems with rebuilding of slow fibers. The observations demonstrate that early nuclear reprogramming with reloading of atrophic soleus muscle is coordinated and links to the processes involved in mechanical damage and regeneration of muscle fibers.
expression profile; microarray; regression; unloading; mechanical stress
Address for reprint requests and other correspondence: M. Flück, Dept. of Anatomy, Univ. of Bern, Baltzerstr. 2, 3000 Bern 9, Switzerland (e-mail: flueck{at}ana.unibe.ch )
1 Department of Anatomy, University of Bern, 3000 Bern 9
2 Nestlé Research Center, Nestec, CH-1000 Lausanne 26
3 Department of Clinical Research (Magnetic Resonance Spectroscopy and Methodology), ...University of Bern and Inselspital Bern, 3010 Bern, Switzerland
It was hypothesized that transcriptional reprogramming is involved in the structural and functional adaptations of lipid metabolism in human tibialis anterior muscle (TA) from endurance-trained male subjects. RT-PCR experiments demonstrated a significant upregulation of the mRNA level of key enzymes involved in 1 ) lipolytic mobilization of fatty acids (FA) from intramyocellular lipid (IMCL) stores via hormone-sensitive lipase (LIPE), 2 ) intramyocellular FA transport via muscle fatty acid binding protein (FABP3), and 3 ) oxidative phosphorylation (cytochrome c oxidase I, COI), in TA of endurance-trained vs. untrained subjects. In contrast, mRNAs for factors involved in glycolysis (muscle 6-phosphofructokinase, PFKM), intramyocellular storage of FA (diacylglycerol O -acyltransferase 1, DGAT), and ß-oxidation (long-chain acyl-coenzyme A dehydrogenase, ACADL) were invariant between TA of trained and untrained subjects. Correlation analysis identified an association of LIPE with FABP3 and LPL (lipoprotein lipase) mRNA levels and indicated coregulation of the transcript level for LIPE, FABP3, and COI with the level of mRNA encoding peroxisome proliferator-activated receptor- (PPAR- ), the master regulator of lipid metabolism. Moreover, a significant correlation existed between LPL mRNA and the absolute rate of IMCL repletion determined by magnetic resonance spectroscopy after exhaustive exercise. Additionally, the LIPE mRNA level correlated with ultrastructurally determined IMCL content and mitochondrial volume density. The present data point to a training-induced, selective increase in mRNA levels of enzymes which are involved in metabolization of intramuscular FA, and these data confirm the well-established phenomenon of enhanced lipid utilization during exercise at moderate intensity in muscles of endurance-trained subjects.
1 H-magnetic resonance spectroscopy; electromagnetic morphometry; gene expression; mRNA; reverse transcriptase-polymerase chain reaction
Institute of Anatomy, University of Bern, Bern, Switzerland
This study investigated the use of the hindlimb suspension (HS) and reloading model of mice for the mapping of ultrastructural and gene ...expressional alterations underlying load-dependent muscular adaptations. Mice were hindlimb suspended for 7 days or kept as controls ( n = 12). Soleus muscles were harvested after HS (HS7, n = 23) or after resuming ambulatory cage activity (reloading) for either 1 day (R1, n = 13) or 7 days (R7, n = 9). Using electron microscopy, a reduction in mean fiber area (37%) and in capillary-to-fiber ratio (from 1.83 to 1.42) was found for HS7. Subsequent reloading caused an increase in interstitial cells (+96%) and in total capillary length (+57%), whereas mean fiber area and capillary-to-fiber ratio did not significantly change compared with HS. Total RNA in the soleus muscle was altered with both HS (63%) and reloading (+108% in R7 compared with control). This is seen as an important adaptive mechanism. Gene expression alterations were assessed by a muscle-specific low-density cDNA microarray. The transcriptional adjustments indicate an early increase of myogenic factors during reloading together with an overshoot of contractile (MyHC I and IIa) and metabolic (glycolytic and oxidative) mRNA amounts and suggest mechano-sensitivity of factors keeping the sarcomeres in register (desmin, titin, integrin-ß1). Important differences to published data from former rat studies were found with the mouse HS model for contractile and glycolytic enzyme expression. These species-specific differences need to be considered when transgenic mice are used for the elucidation of monogenetic factors in mechano-dependent muscle plasticity.
unloading; mechanical loading; simulated microgravity; gene expression; rat
Since muscle mass makes up such a high proportion of total body mass, there must have been considerable selective pressure to minimize the cost of maintenance and to maximize the functionality of ...muscle tissue for all species. Phenotypic plasticity of muscle tissue allows the species blueprint of muscle tissue to be modified to accommodate specific demands experienced by animals over their lifetime. In this review, we report the scaling of muscle structural compartments in a set of mammals spanning five orders of magnitude (17 g woodmice to 450 kg horses and steers). Muscle mass, muscle myofibrillar volume and sarcoplasmic space were found to represent similar relative quantities in all species studies (scaling factor close to unity). Mitochondrial volumes were found to be systematically smaller in larger animals (scaling factor 0.91) and closely related to the scaling of (O(2)max) (0.92) and were tracked by the scaling of total capillary length (0.95). In this set of species, we therefore found that maximal metabolic rate and supporting structures did not scale to the 0.75 power of body mass as generally suggested. Muscle phenotypic plasticity is reasonably well characterized on a structural and functional basis, but we still know little about the signals that cause the changes in gene expression necessary for phenotypic changes in muscle. The molecular responses of human m. vastus lateralis to endurance exercise indicate that a single bout of exercise causes specific transient transcriptional adaptations that may gradually accumulate after their translation into the (structural) modifications seen with phenotypic plasticity. Metabolic and mechanical factors are recognized candidate factors for the control of exercise-induced gene transcription in muscle. Distinct protein kinases and transcription factors emerge as possible interfaces that integrate the mechanical (MAPKs and jun/fos) and metabolic (AMPK, HIF-1alpha and PPARalpha) stimuli into enhanced gene transcription in skeletal muscle.
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