Project description:Aim: To examine the global gene expression response to the profound metabolic and hormonal stress induced by acute sprint exercise. Methods: Healthy women and men (n=14) performed 3 all-out cycle sprints interspersed by 20 min recovery. Muscle biopsies were obtained before the first and 2h and 20 min after the last sprint. Microarray analysis was performed to analyse the acute gene expression response. Repeated blood sample were also obtained. Results: In skeletal muscle, a set of immediate early genes, FOS, NR4A3, MAFF, EGR1, JUNB were markedly upregulated after sprint exercise. These genes were also upregulated, but to a lesser extent, after other exercise modes and after insulin exposure. Gene ontology analysis from 879 differentially expressed genes revealed predicted activation of extracellular remodelling and fat metabolism, which was in common with the gene expression response to endurance and resistance exercise. Moreover, the gene expression pattern indicated an increased turnover of skeletal muscle mass after sprint exercise, which was in common with data on resistance exercise and GH exposure. Insulin and GH may be involved in sprint-induced changes in the transcriptome, based on the overlap noted between sprint- and hormone exposure-related signatures. Furthermore, there were correlations between sprint-induced changes in hormonal levels and changes in gene expression. Conclusion: This is the first study reporting on global gene expression in skeletal muscle in response to acute sprint exercise. Several novel findings are presented related to novel sprint exercise - regulated genes as well as to shared gene signatures between sprint exercise, other exercise modes and exogenous hormone exposure.
Project description:Global microarray (HG U133 Plus 2.0) was used to investigate the effects of resistance exercise and resistance training on the skeletal muscle transcriptome profile of 28 young and old adults. Vastus lateralis muscle biopsies were obtained pre and 4hrs post resistance exercise in the beginning (untrained state) and at the end (trained state) of a 12 wk progressive resistance training program.
Project description:Analysis of gene expression associated with exercise response. The hypothesis tested was that individuals with Type 2 Diabetes that failed to demonstrate exercise-induced metabolic improvements would also reflect this lack of response in their skeletal muscle transcriptional profile at baseline. Of 186 genes identified by microarray analysis, 70% were upregulated in Responders and downregulated in Non-responders. Several genes involved in substrate metabolism and mitochondrial biogenesis differed significantly between the groups at baseline. This differential baseline gene expression indicated that Non-responders had blunted oxidative capacity. Total RNA extracted from baseline samples of skeletal muscle of obese individuals with Type 2 Diabetes who were characterized as either Responders or Non-responders was examined for differential expression of exercise response-assocated genes.
Project description:Human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia). Multiple lines of evidence suggest that mitochondrial dysfunction is a major contributor to sarcopenia. We evaluated whether healthy aging was associated with a transcriptional profile reflecting mitochondrial impairment and whether resistance exercise could reverse this signature to that approximating a younger physiological age. Skeletal muscle biopsies from healthy older (N = 25) and younger (N = 26) adult men and women were compared using gene expression profiling, and a subset of these were related to measurements of muscle strength. 14 of the older adults had muscle samples taken before and after a six-month resistance exercise-training program. Before exercise training, older adults were 59% weaker than younger, but after six months of training in older adults, strength improved significantly (P<0.001) such that they were only 38% lower than young adults. As a consequence of age, we found 596 genes differentially expressed using a false discovery rate cut-off of 5%. Prior to the exercise training, the transcriptome profile showed a dramatic enrichment of genes associated with mitochondrial function with age. However, following exercise training the transcriptional signature of aging was markedly reversed back to that of younger levels for most genes that were affected by both age and exercise. We conclude that healthy older adults show evidence of mitochondrial impairment and muscle weakness, but that this can be partially reversed at the phenotypic level, and substantially reversed at the transcriptome level, following six months of resistance exercise training. Keywords: resistance exercise, muscle, aging
Project description:Analysis of skeletal muscle gene expression from type 2 diabetic volunteers before and after 16 weeks of chronic exercise training (two groups, one undergoing aerobic ecercise and the other resistance training exercise)
Project description:Exercise training increases endurance by inducing global gene expression changes in skeletal muscles. The extent to which the genetic effects of exercise can be mimicked by synthetic drugs is unknown. We measured global skeletal muscle expression in sedentary and exercised mice treated with vehicle or PPARdelta ligand GW1516. PPARdelta is a transcriptional regulator of muscle oxidative metabolism and fatigue resistance. Keywords: Pharmacology study
Project description:The molecular mechanisms underlying the sex differences in human muscle morphology and function remain to be elucidated. The purpose of the study was to detect the sex differences in the skeletal muscle transcriptome in both the resting state and following anabolic stimuli, resistance exercise. We used microarrays to profile the transcriptome of the biceps brachii of young men and women who underwent an acute unilateral RE session following 12 weeks of progressive training. Bilateral muscle biopsies were obtained either at an early (4h post-exercise) or late recovery (24h post-exercise) time point. Muscle transcription profiles were compared in the resting state between men (n=6) and women (n=8), and in response to acute RE in trained exercised vs. untrained non-exercised control muscle for each sex and time point separately (4h post-exercise, n=3 males, n=4 females; 24h post-exercise, n=3 males, n=4 females). A logistic regression-based method (LRpath), following Bayesian moderated t-statistic (IMBT), was used to test gene functional groups and biological pathways enriched with differentially expressed genes.
Project description:Exercise training increases endurance by inducing global gene expression changes in skeletal muscles. The extent to which the genetic effects of exercise can be mimicked by synthetic drugs is unknown. We measured global skeletal muscle expression in sedentary and exercised mice treated with vehicle or PPARdelta ligand GW1516. PPARdelta is a transcriptional regulator of muscle oxidative metabolism and fatigue resistance. Experiment Overall Design: Sedentary and exercise trained C57Bl/6J mice were treated with vehicle or GW1516 for 4 weeks, followed by collection of quadriceps for gene expression analysis.
Project description:High fat feeding is deleterious for skeletal muscle metabolism, while exercise has well documented beneficial effects for these same metabolic features. To identify the genomic mechanisms by which exercise ameliorates some of the deleterious effects of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression (by RNA-seq) and DNA methylation (by Reduced Representation Bisulfite Sequencing). HFD markedly induced expression of immune and inflammatory genes which was not attenuated by Ex. In contract, Ex markedly remodelled expression of genes associated with muscle growth and structure. We detected marked DNA methylation changes following HFD alone and in combination with Ex. Among the genes that showed significant association between DNA methylation changes and gene expression were glycogen phosphorylase, muscle associated (PYGM), which was epigenetically regulated in both groups, and angiopoiten like 4 (ANGPTL4), which was regulated only following Ex. We conclude that Short-term Ex does not prevent HFD-induced inflammatory response, but provokes a genomic response that may preserve skeletal muscle from atrophy. Epigenetic adaptation provides important mechanistic insight into the gene specific regulation of inflammatory and metabolic processes in human skeletal muscle.