Response of muscle protein turnover to insulin after acute exercise and training.
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ABSTRACT:
SUBMITTER: Davis TA
PROVIDER: S-EPMC1147470 | biostudies-other | 1986 Dec
REPOSITORIES: biostudies-other
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Project description:The athletic horse, despite being over 50% muscle mass, remains understudied with regard to the effects of exercise and training on skeletal muscle metabolism. To begin to address this knowledge gap, we employed an untargeted metabolomics approach to characterize the exercise-induced and fitness-related changes in the skeletal muscle of eight unconditioned Standardbred horses (four male, four female) before and after a 12-week training period. Before training, unconditioned horses showed a high degree of individual variation in the skeletal muscle metabolome, resulting in very few differences basally and at 3 and 24 h after acute fatiguing exercise. Training did not alter body composition but did improve maximal aerobic and running capacities (p < 0.05), and significantly altered the skeletal muscle metabolome (p < 0.05, q < 0.1). While sex independently influenced body composition and distance run following training (p < 0.05), sex did not affect the skeletal muscle metabolome. Exercise-induced metabolomic alterations (p < 0.05, q < 0.1) largely centered on the branched-chain amino acids (BCAA), xenobiotics, and a variety of lipid and nucleotide-related metabolites, particularly in the conditioned state. Further, training increased (p < 0.05, q < 0.1) the relative abundance of almost every identified lipid species, and this was accompanied by increased plasma BCAAs (p < 0.0005), phenylalanine (p = 0.01), and tyrosine (p < 0.02). Acute exercise in the conditioned state decreased (p < 0.05, q < 0.1) the relative abundance of almost all lipid-related species in skeletal muscle by 24 h post-exercise, whereas plasma amino acids remained unaltered. These changes occurred alongside increased muscle gene expression (p < 0.05) related to lipid uptake (Cd36) and lipid (Cpt1b) and BCAA (Bckdk) utilization. This work suggests that metabolites related to amino acid, lipid, nucleotide and xenobiotic metabolism play pivotal roles in the response of equine skeletal muscle to vigorous exercise and training. Use of these and future data sets could be used to track the impact of training and fitness on equine health and may lead to novel predictors and/or diagnostic biomarkers.
| S-EPMC7040365 | biostudies-literature
Project description:The etiology of insulin resistance in Type 1 Diabetes (T1D) is unknown, however it affects approximately 20% of T1D patients. Intramyocellular lipids (IMCL) have been identified as a mechanism of insulin resistance. We examined skeletal muscle of T1D rats to determine if alterations in lipid metabolism were evident and whether aerobic exercise training improves IMCL and insulin resistance. To do so, 48 male Sprague-Dawley rats were divided into control (C), sedentary diabetes (D) and diabetes exercise (DX) groups. Following multiple low-dose Streptozotocin (STZ) injections (20 mg/kg), glycemia (9-15 mM) was maintained using insulin treatment. DX were treadmill trained at high intensity (~75% V02max; 5days/week) for 10 weeks. The results demonstrate that D exhibited insulin resistance compared with C and DX, indicated by decreased glucose infusion rate during a hyperinsulinemic-euglycemic clamp (p < 0.05). There were no differences between C and DX, suggesting that exercise improved insulin resistance (p < 0.05). Metabolomics analysis revealed a significant shift in lipid metabolism whereby notable fatty acid metabolites (arachidonic acid, palmitic acid and several polyunsaturated fatty acids) were significantly elevated in D compared to C and DX. Based on the intermediates observed, insulin resistance in T1D is characterized by an insulin-desensitizing intramyocellular fatty acid metabolite profile that is ameliorated with exercise training.
| S-EPMC4873835 | biostudies-other
Project description:BackgroundExacerbations in COPD are often accompanied by pulmonary and systemic inflammation, and associated with increased susceptibility to and prevalence of weight loss and muscle wasting. Muscle mass loss during disease exacerbations may contribute to emphysema-associated muscle atrophy. However, whether pulmonary inflammation in presence of emphysema differentially affects skeletal muscle, including protein synthesis and degradation signaling pathways has not previously been addressed. The aims of this study were to 1) develop a mouse model of disease exacerbation-associated muscle wasting, 2) evaluate whether emphysema and muscle wasting can be monitored non-invasively and 3) assess alterations in muscle protein turnover regulation.MethodsEmphysema was induced by three, weekly intra-tracheal (IT) elastase (E) or vehicle control (vc) instillations, followed by one single IT-LPS bolus (L) or vc instillation to mimic pulmonary inflammation-driven disease exacerbation. Consequently, four experimental groups were defined: vc/vc ('C'), E/vc ('E'), vc/LPS ('L'), E/LPS ('E + L'). Using micro cone-beam CT-scans, emphysema development and muscle mass changes were monitored, and correlated to muscle weight 48 h after LPS instillation. Protein turnover signaling was assessed in muscle tissue collected 24 h post LPS instillation.ResultsMicro-CT imaging correlated strongly with established invasive measurements of emphysema and muscle atrophy. Pulmonary inflammation following LPS instillation developed irrespective of emphysema and body and muscle weight were similarly reduced in the 'L' and 'E + L' groups. Accordingly, mRNA and protein expression levels of genes of the ubiquitin-proteasome pathway (UPS) and the autophagy-lysosomal pathway (ALP) were upregulated in skeletal muscle following IT-LPS ('L' and 'E + L'). In contrast, mTOR signaling, which controls ALP and protein synthesis, was reduced by pulmonary inflammation ('L' and 'E + L') as well as emphysema as a single insult ('E') compared to control.ConclusionChanges in lung tissue density and muscle mass can be monitored non-invasively to evaluate emphysema and muscle atrophy longitudinally. Acute loss of muscle mass evoked by pulmonary inflammation is similar in control and emphysematous mice. Although muscle atrophy cues in response to pulmonary inflammation are not altered by emphysema, emphysema itself affects protein synthesis and ALP signaling, which may interfere with muscle mass recovery and impair maintenance of muscle mass in emphysema.
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Project description:In our study, we investigated for contractile activity-specific changes in the transcriptome in untrained and trained (after an aerobic training programme) human skeletal muscle. The second goal was to examine effect of aerobic training on gene expression in muscle at baseline (after long term training). Seven untrained males performed the one-legged knee extension exercise (for 60 min) with the same relative intensity before and after a 2 month aerobic training programme (1 h/day, 5/week). Biopsy samples were taken at rest (baseline condition, 48 h after exercise), 1 and 4 h after the one-legged exercise from m. vastus lateralis of either leg. Comparison of gene expression in exercised leg with that in non-exercised [control] leg allowed us to identify contractile activity-specific genes in both untrained and trained skeletal muscle, i.e., genes that play a key role in adapting to acute exercise, regardless of the level of fitness. RNA-sequencing (84 samples in total; ~47 million reads/sample) was performed by NextSeq 500 and HiSeq 2500 (Illumina). Two months aerobic training increased the aerobic capacity of the knee-extensor muscles (power at anaerobic threshold in the incremental one-legged and cycling tests), the maximum rate of ADP-stimulated mitochondrial respiration in permeabilized muscle fibres and amounts of oxidative phosphorylation proteins. Contractile activity-specific changes in the transcriptome in untrained and trained human skeletal muscle were revealed for the first time. After 2 month aerobic training, transcriptome responses specific for contractile activity in trained muscle substantially decreased relative to those in untrained muscle. We found out that adaptation of skeletal muscle to regular exercise is associated not only with a transient change in the transcriptome after each stress (acute exercise), but also with a marked change in baseline expression of many genes after repeated stress (e.g., long term training).
2019-02-16 | GSE120862 | GEO
Project description:Defects in mitochondrial dynamics, the processes of fission, fusion, and mitochondrial autophagy, may contribute to metabolic disease including type 2 diabetes. Dynamin-related protein-1 (Drp1) is a GTPase protein that plays a central role in mitochondrial fission. We hypothesized that aerobic exercise training would decrease Drp1 Ser(616) phosphorylation and increase fat oxidation and insulin sensitivity in obese (body mass index: 34.6 ± 0.8 kg/m(2)) insulin-resistant adults. Seventeen subjects performed supervised exercise for 60 min/day, 5 days/wk at 80-85% of maximal heart rate for 12 wk. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and fat oxidation was determined by indirect calorimetry. Skeletal muscle biopsies were obtained from the vastus lateralis muscle before and after the 12-wk program. The exercise intervention increased insulin sensitivity 2.1 ± 0.2-fold (P < 0.01) and fat oxidation 1.3 ± 0.3-fold (P < 0.01). Phosphorylation of Drp1 at Ser(616) was decreased (pre vs. post: 0.81 ± 0.15 vs. 0.58 ± 0.14 arbitrary units; P < 0.05) following the intervention. Furthermore, reductions in Drp1 Ser(616) phosphorylation were negatively correlated with increases in fat oxidation (r = -0.58; P < 0.05) and insulin sensitivity (rho = -0.52; P < 0.05). We also examined expression of genes related to mitochondrial dynamics. Dynamin1-like protein (DNM1L; P < 0.01), the gene that codes for Drp1, and Optic atrophy 1 (OPA1; P = 0.05) were significantly upregulated following the intervention, while there was a trend towards an increase in expression of both mitofusin protein MFN1 (P = 0.08) and MFN2 (P = 0.07). These are the first data to suggest that lifestyle-mediated improvements in substrate metabolism and insulin sensitivity in obese insulin-resistant adults may be regulated through decreased activation of the mitochondrial fission protein Drp1.
| S-EPMC4122691 | biostudies-literature
Project description:: Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.
| S-EPMC7073171 | biostudies-literature
Project description:Acute bouts of resistance exercise and subsequent training alters protein turnover in skeletal muscle. The mechanisms responsible for the changes in basal post-absorptive protein turnover and its impact on muscle hypertrophy following resistance exercise training are unknown. Our goal was to determine whether post-absorptive muscle protein turnover following 12 weeks of resistance exercise training (RET) plays a role in muscle hypertrophy. In addition, we were interested in determining potential molecular mechanisms responsible for altering post-training muscle protein turnover.Healthy young men (n?=?31) participated in supervised whole body progressive RET at 60-80% 1 repetition maximum (1-RM), 3 days/week for 3 months. Pre- and post-training vastus lateralis muscle biopsies and blood samples taken during an infusion of 13C6 and 15N phenylalanine and were used to assess skeletal muscle protein turnover in the post-absorptive state. Lean body mass (LBM), muscle strength (determined by dynamometry), vastus lateralis muscle thickness (MT), myofiber type-specific cross-sectional area (CSA), and mRNA were assessed pre- and post-RET.RET increased strength (12-40%), LBM (~5%), MT (~15%) and myofiber CSA (~20%) (p?<?0.05). Muscle protein synthesis (MPS) increased 24% while muscle protein breakdown (MPB) decreased 21%, respectively. These changes in protein turnover resulted in an improved net muscle protein balance in the basal state following RET. Further, the change in basal MPS is positively associated (r?=?0.555, p?=?0.003) with the change in muscle thickness.Post-absorptive muscle protein turnover is associated with muscle hypertrophy during resistance exercise training.
| S-EPMC5389914 | biostudies-other
Project description:AIM:To determine the genomic mechanisms by which adipose tissue responds to acute and chronic exercise. METHODS:We profiled the transcriptomic and epigenetic response to acute exercise in human adipose tissue collected before and after endurance training. RESULTS:Although acute exercises were performed at same relative intensities, the magnitude of transcriptomic changes after acute exercise was reduced by endurance training. DNA methylation remodeling induced by acute exercise was more prominent in trained versus untrained state. We found an overlap between gene expression and DNA methylation changes after acute exercise for 32 genes pre-training and six post-training, notably at adipocyte-specific genes. CONCLUSION:Training status differentially affects the epigenetic and transcriptomic response to acute exercise in human adipose tissue.
| S-EPMC6190185 | biostudies-literature
Project description:Bulk polyA-RNAseq was performed on vastus lateralis muscle samples from older adults ≥65y at baseline and post-14 wk resistance exercise training (high-low-high intensity). The primary study used network biology algorithms to create gene networks of highly connected transcripts, and then linked these to change in muscle size induced by exercise training.
2021-06-01 | GSE163434 | GEO
Project description:DNA methylation is an important epigenetic modification that can regulate gene expression following environmental encounters without changes to the genetic code. Using Infinium MethylationEPIC BeadChip Arrays (850,000 CpG sites) we analysed for the first time, DNA isolated from untrained human skeletal muscle biopsies (vastus lateralis) at baseline (rest) and immediately following an acute (single) bout of resistance exercise. In the same participants, we also analysed the methylome following a period of muscle growth (hypertrophy) evoked via chronic (repeated bouts-3 sessions/wk) resistance exercise (RE) (training) over 7-weeks, followed by complete exercise cessation for 7-weeks returning muscle back to baseline levels (detraining), and finally followed by a subsequent 7-week period of RE-induced hypertrophy (retraining). These valuable methylome data sets described in the present manuscript and deposited in an open-access repository can now be shared and re-used to enable the identification of epigenetically regulated genes/networks that are modified after acute anabolic stimuli and hypertrophy, and further investigate the phenomenon of epigenetic memory in skeletal muscle.
| S-EPMC6207066 | biostudies-literature