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PGC-1 isoforms and their target genes are expressed differently in human skeletal muscle following resistance and endurance exercise.

ABSTRACT: The primary aim of the present study was to investigate the acute gene expression responses of PGC-1 isoforms and PGC-1? target genes related to mitochondrial biogenesis (cytochrome C), angiogenesis (VEGF-A), and muscle hypertrophy (myostatin), after a resistance or endurance exercise bout. In addition, the study aimed to elucidate whether the expression changes of studied transcripts were linked to phosphorylation of AMPK and MAPK p38. Nineteen physically active men were divided into resistance exercise (RE, n = 11) and endurance exercise (EE, n = 8) groups. RE group performed leg press exercise (10 × 10 RM, 50 min) and EE walked on a treadmill (~80% HRmax, 50 min). Muscle biopsies were obtained from the vastus lateralis muscle before, 30 min, and 180 min after exercise. EE and RE significantly increased the gene expression of alternative promoter originated PGC-1? exon 1b- and 1bxs'-derived isoforms, whereas the proximal promoter originated exon 1a-derived transcripts were less inducible and were upregulated only after EE. Truncated PGC-1? transcripts were upregulated both after EE and RE. Neither RE nor EE affected the expression of PGC-1?. EE upregulated the expression of cytochrome C and VEGF-A, whereas RE upregulated VEGF-A and downregulated myostatin. Both EE and RE increased the levels of p-AMPK and p-MAPK p38, but these changes were not linked to the gene expression responses of PGC-1 isoforms. The present study comprehensively assayed PGC-1 transcripts in human skeletal muscle and showed exercise mode-specific responses thus improving the understanding of early signaling events in exercise-induced muscle adaptations.

SUBMITTER: Silvennoinen M

PROVIDER: S-EPMC4632948 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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PGC-1 isoforms and their target genes are expressed differently in human skeletal muscle following resistance and endurance exercise.

Silvennoinen Mika M Ahtiainen Juha P JP Hulmi Juha J JJ Pekkala Satu S Taipale Ritva S RS Nindl Bradley C BC Laine Tanja T Häkkinen Keijo K Selänne Harri H Kyröläinen Heikki H Kainulainen Heikki H

Physiological reports 20151001 10

The primary aim of the present study was to investigate the acute gene expression responses of PGC-1 isoforms and PGC-1α target genes related to mitochondrial biogenesis (cytochrome C), angiogenesis (VEGF-A), and muscle hypertrophy (myostatin), after a resistance or endurance exercise bout. In addition, the study aimed to elucidate whether the expression changes of studied transcripts were linked to phosphorylation of AMPK and MAPK p38. Nineteen physically active men were divided into resistance ...[more]

PMID: 26438733

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Project description:Skeletal muscle metabolic function is known to respond positively to exercise interventions. Developing non-invasive techniques that quantify metabolic adaptations and identifying interventions that impart successful response are ongoing challenges for research. Healthy non-athletic adults (18-35 years old) were enrolled in a study investigating physiological adaptations to a minimum of 16 weeks endurance training prior to undertaking their first marathon. Before beginning training, participants underwent measurements of skeletal muscle oxygen consumption using near-infrared spectroscopy (NIRS) at rest (resting muscle[Formula: see text]O2) and immediately following a maximal exercise test (post-exercise muscle[Formula: see text]O2). Exercise-related increase in muscle[Formula: see text]O2 (Δm[Formula: see text]O2) was derived from these measurements and cardio-pulmonary peak[Formula: see text]O2 measured by analysis of expired gases. All measurements were repeated within 3 weeks of participants completing following the marathon and marathon completion time recorded. Muscle[Formula: see text]O2 was positively correlated with cardio-pulmonary peak[Formula: see text]O2 (r = 0.63, p < 0.001). Muscle[Formula: see text]O2 increased at follow-up (48% increase; p = 0.004) despite no change in cardio-pulmonary peak[Formula: see text]O2 (0% change; p = 0.97). Faster marathon completion time correlated with higher cardio-pulmonary peak[Formula: see text]O2 (rpartial = -0.58, p = 0.002) but not muscle[Formula: see text]O2 (rpartial = 0.16, p = 0.44) after adjustment for age and sex [and adipose tissue thickness (ATT) for muscle[Formula: see text]O2 measurements]. Skeletal muscle metabolic adaptions occur following training and completion of a first-time marathon; these can be identified non-invasively using NIRS. Although the cardio-pulmonary system is limiting for running performance, skeletal muscle changes can be detected despite minimal improvement in cardio-pulmonary function.

Project description:Background: Muscle responses to exercise are complex, and potentially include acute responses to exercise-induced injury as well as longer-term adaptive training responses. Using Alaskan sled dogs as an experimental model, changes in muscle gene expression were analyzed to better understand the temporal changes that occur after severe exercise. Methods: Dogs were randomly assigned to undertake in a 160 km run (n=9), or to remain at rest (n=4). Biceps femoris muscle was obtained by needle biopsy from the unexercised dogs and two dogs at each of 2, 6 and 12 hours after the exercise and from 3 dogs 24 hours after exercise. RNA was extracted and microarray analysis used to define gene transcriptional changes. Results: Nine hundred sixty three transcripts exhibited statistically significant change over time after exercise as compared to the unexercised dogs. The changes in gene expression after exercise occurred in a clear temporal pattern and included transcripts with increased expression 2 hours after exercise with a return towards resting levels by 6 hours after exercise. Other transcripts demonstrated increased expression which peaked at six hours after exercise, while other transcripts showed sustained induction or repression over the 24 hours after exercise. Increases in a number of known transcriptional regulators, including PPAR-Î±, CERM and CEBPD, were observed 2-hours after exercise. Pathway analysis demonstrated coordinated changes in expression of genes with known functional relationships, including genes involved in muscle remodeling and growth, intermediary metabolism and immune regulation. Conclusion: Sustained endurance exercise by Alaskan sled dogs induces coordinated changes in gene expression with a clear temporal pattern. RNA expression profiling has the potential to identify novel regulatory mechanisms and responses to exercise stimuli. Subjects were 13 Alaskan sled dogs aged 4.5 + 2.5 years (mean + SD) and weighing 23.3 + 2.5 kg. Dogs were randomly assigned to two groups â one group of 9 dogs subsequently ran 160 km in 24 hours as 2 sessions of 80 km, separated by a 6 hour rest period. The second group consisted of four dogs housed in unheated kennels, their usual housing, for the duration of the experiment. All dogs were from the same kennel. Dogs were fed a commercial kibble (Eukanuba, Iams Company, Dayton, OH) supplemented with frozen meat during the 8 weeks preceding the study and throughout the study period. The dogâs diet was consistent before, during and after the exercise bout. All dogs had completed 1590 + 100 km of training runs in the 3 months before the study. The dogs had not exercised for 72 hors before the start of this study. Dogs in the exercise group ran as a team pulling a lightly laden sled and driver over packed snow. Ambient temperatures were -20o to -10o C with no wind. Dogs completed the two 80 km runs in 23 hours, including the 6 hour rest period. Blood samples were collected by jugular venepuncture from all dogs the day before exercise, and within a 10 minute window at 2, 6, 12, and 24 hours after completing the second run. Samples were collected into evacuated glass tubes containing a clot enhancer. Muscle samples were collected from each of two dogs within a 10 minute window at 2, 6 and 12 hours after completing exercise and from three dogs 24 hours after completing exercise. Muscle samples were collected from each of the four unexercised dogs within two hours of the other dogs initiating their exercise bout. Each dog had only one biopsy procedure performed. Muscle samples were collected from the biceps femoris muscle using a needle biopsy that yielded approximately 40-60 mg of muscle. The biopsy was performed after clipping and aseptic preparation of the skin overlying the biopsy site. The dog was anesthetized with propofol (6 mg/kg, IV, maintained as necessary with 2 mg/kg additional boluses), a cuffed orotracheal tube placed and the dog ventilated with a hand-held ventilation bag. When adequate anesthesia had been obtained a 5 mm incision was made in the skin. A sterile biopsy needle (12 g PGI EZ Core, Products group International, Inc. Lyons, CO) was then inserted through the incision and a sample of muscle collected. If necessary, repeated collections of muscle were made until a minimum of 40 mg of muscle has been collected from an individual dog. The skin incision was closed with tissue glue and an antibiotic ointment applied. The dog was monitored closely until recovery from anesthesia was complete. Carprofen (4.4 mg/kg, orally) was administered when the dog had recovered sufficiently from anesthesia to have a gag reflex.

Dataset Information

PGC-1 isoforms and their target genes are expressed differently in human skeletal muscle following resistance and endurance exercise.

Publications

PGC-1 isoforms and their target genes are expressed differently in human skeletal muscle following resistance and endurance exercise.

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