| 1. |
- Emanuelsson, Eric B., et al.
(författare)
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MRI characterization of skeletal muscle size and fatty infiltration in long--term trained and untrained individuals
- 2022
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 54:9, s. 389-389
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated body composition measures in highly trained and untrained individuals using whole--body magnetic resonance imaging (MRI). Additionally, correlations between these measures and skeletal muscle gene expression were performed. Thirty-six individuals were included: endurance-trained males (ME, n = 8) and females (FE, n = 7), strength-trained males (MS, n = 7), and untrained control males (MC, n = 8) and females (FC, n = 6). MRI scans were performed, and resting M. vastus lateralis (VL) biopsies were subjected to RNA sequencing. Liver fat fraction, visceral adipose tissue volume (VAT), total body fat, and total lean tissue were measured from MRI data. Additionally, cross-sectional area (CSA) and fat signal fraction (FSF) were calculated from Mm. pectoralis, M. erector spinae and M. multifidus combined, Mm. quadriceps, and Mm. triceps surae (TS). Liver fat fraction, VAT, and total body fat relative to body weight were lower in ME and FE compared with corresponding controls. MS had a larger CSA across all four muscle groups and lower FSF in all muscles apart from TS compared with MC. ME had a lower FSF across all muscle groups and a larger CSA in all muscles except TS than MC. FE athletes showed a higher CSA in Mm. pectoralis and Mm. quadriceps and a lower CSA in TS than FC with no CSA differences found in the back muscles investigated. Surprisingly, the only difference in FSF between FE and FC was found in Mm. pectoralis. Lastly, correlations between VL gene expression and VL CSA as well as FSF showed that genes positively correlated with CSA revealed an enrichment of the oxidative phosphorylation and thermogenesis pathways, while the genes positively correlated with FSF showed significant enrichment of the spliceosome pathway. Although limited differences were found with training in females, our study suggests that both regular endurance and resistance training are useful in maintaining muscle mass, reducing adipose tissue deposits, and reducing muscle fat content in males.
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| 2. |
- Chapman, Mark A., et al.
(författare)
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Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and Women
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 31:12
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Tidskriftsartikel (refereegranskat)abstract
- To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases, This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important "exercise-responsive" genes that could attenuate metabolic disease.
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| 3. |
- Emanuelsson, Eric B., et al.
(författare)
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Remodeling of the human skeletal muscle proteome found after long-term endurance training but not after strength training
- 2024
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- Exercise training has tremendous systemic tissue-specific health benefits, but the molecular adaptations to long-term exercise training are not completely understood. We investigated the skeletal muscle proteome of highly endurance-trained, strength-trained, and untrained individuals and performed exercise- and sex-specific analyses. Of the 6,000+ proteins identified, >650 were differentially expressed in endurance-trained individuals compared with controls. Strikingly, 92% of the shared proteins with higher expression in both the male and female endurance groups were known mitochondrial. In contrast to the findings in endurance-trained individuals, minimal differences were found in strength-trained individuals and between females and males. Lastly, a co-expression network and comparative literature analysis revealed key proteins and pathways related to the health benefits of exercise, which were primarily related to differences in mitochondrial proteins. This network is available as an interactive database resource where investigators can correlate clinical data with global gene and protein expression data for hypothesis generation.
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| 4. |
- Lindskog, Cecilia, et al.
(författare)
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The human cardiac and skeletal muscle proteomes defined by transcriptomics and antibody-based profiling
- 2015
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: To understand cardiac and skeletal muscle function, it is important to define and explore their molecular constituents and also to identify similarities and differences in the gene expression in these two different striated muscle tissues. Here, we have investigated the genes and proteins with elevated expression in cardiac and skeletal muscle in relation to all other major human tissues and organs using a global transcriptomics analysis complemented with antibody-based profiling to localize the corresponding proteins on a single cell level. Results: Our study identified a comprehensive list of genes expressed in cardiac and skeletal muscle. The genes with elevated expression were further stratified according to their global expression pattern across the human body as well as their precise localization in the muscle tissues. The functions of the proteins encoded by the elevated genes are well in line with the physiological functions of cardiac and skeletal muscle, such as contraction, ion transport, regulation of membrane potential and actomyosin structure organization. A large fraction of the transcripts in both cardiac and skeletal muscle correspond to mitochondrial proteins involved in energy metabolism, which demonstrates the extreme specialization of these muscle tissues to provide energy for contraction. Conclusions: Our results provide a comprehensive list of genes and proteins elevated in striated muscles. A number of proteins not previously characterized in cardiac and skeletal muscle were identified and localized to specific cellular subcompartments. These proteins represent an interesting starting point for further functional analysis of their role in muscle biology and disease.
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| 5. |
- Reitzner, Stefan M., et al.
(författare)
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Molecular profiling of high-level athlete skeletal muscle after acute endurance or resistance exercise : A systems biology approach
- 2024
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Ingår i: Molecular Metabolism. - : Elsevier GmbH. - 2212-8778. ; 79
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Long-term high-level exercise training leads to improvements in physical performance and multi-tissue adaptation following changes in molecular pathways. While skeletal muscle baseline differences between exercise-trained and untrained individuals have been previously investigated, it remains unclear how training history influences human multi-omics responses to acute exercise. Methods: We recruited and extensively characterized 24 individuals categorized as endurance athletes with >15 years of training history, strength athletes or control subjects. Timeseries skeletal muscle biopsies were taken from M. vastus lateralis at three time-points after endurance or resistance exercise was performed and multi-omics molecular analysis performed. Results: Our analyses revealed distinct activation differences of molecular processes such as fatty- and amino acid metabolism and transcription factors such as HIF1A and the MYF-family. We show that endurance athletes have an increased abundance of carnitine-derivates while strength athletes increase specific phospholipid metabolites compared to control subjects. Additionally, for the first time, we show the metabolite sorbitol to be substantially increased with acute exercise. On transcriptional level, we show that acute resistance exercise stimulates more gene expression than acute endurance exercise. This follows a specific pattern, with endurance athletes uniquely down-regulating pathways related to mitochondria, translation and ribosomes. Finally, both forms of exercise training specialize in diverging transcriptional directions, differentiating themselves from the transcriptome of the untrained control group. Conclusions: We identify a “transcriptional specialization effect” by transcriptional narrowing and intensification, and molecular specialization effects on metabolomic level Additionally, we performed multi-omics network and cluster analysis, providing a novel resource of skeletal muscle transcriptomic and metabolomic profiling in highly trained and untrained individuals.
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| 6. |
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| 7. |
- Timmons, James A., et al.
(författare)
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Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans
- 2010
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 108:6, s. 1487-1496
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Tidskriftsartikel (refereegranskat)abstract
- Timmons JA, Knudsen S, Rankinen T, Koch LG, Sarzynski M, Jensen T, Keller P, Scheele C, Vollaard NB, Nielsen S, Akerstrom T, MacDougald OA, Jansson E, Greenhaff PL, Tarnopolsky MA, van Loon LJ, Pedersen BK, Sundberg CJ, Wahlestedt C, Britton SL, Bouchard C. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol 108: 1487-1496, 2010. First published February 4, 2010; doi:10.1152/japplphysiol.01295.2009.-A low maximal oxygen consumption ((V) over dotO(2max)) is a strong risk factor for premature mortality. Supervised endurance exercise training increases (V) over dotO(2max) with a very wide range of effectiveness in humans. Discovering the DNA variants that contribute to this heterogeneity typically requires substantial sample sizes. In the present study, we first use RNA expression profiling to produce a molecular classifier that predicts (V) over dotO(2max) training response. We then hypothesized that the classifier genes would harbor DNA variants that contributed to the heterogeneous (V) over dotO(2max) response. Two independent preintervention RNA expression data sets were generated (n = 41 gene chips) from subjects that underwent supervised endurance training: one identified and the second blindly validated an RNA expression signature that predicted change in (V) over dotO(2max) (""predictor"" genes). The HERITAGE Family Study (n = 473) was used for genotyping. We discovered a 29-RNA signature that predicted (V) over dotO(2max) training response on a continuous scale; these genes contained similar to 6 new single-nucleotide polymorphisms associated with gains in (V) over dotO(2max) in the HERITAGE Family Study. Three of four novel candidate genes from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e., ""reciprocal"" RNA validation of a quantitative trait locus genotype), enhancing the performance of the 29-RNA-based predictor. Notably, RNA abundance for the predictor genes was unchanged by exercise training, supporting the idea that expression was preset by genetic variation. Regression analysis yielded a model where 11 single-nucleotide polymorphisms explained 23% of the variance in gains in (V) over dotO(2max), corresponding to similar to 50% of the estimated genetic variance for (V) over dotO(2max). In conclusion, combining RNA profiling with single-gene DNA marker association analysis yields a strongly validated molecular predictor with meaningful explanatory power. (V) over dotO(2max) responses to endurance training can be predicted by measuring a similar to 30-gene RNA expression signature in muscle prior to training. The general approach taken could accelerate the discovery of genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of physiological and pharmacological phenotypes in humans.
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| 8. |
- Vollaard, Niels B. J., et al.
(författare)
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Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance
- 2009
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 106:5, s. 1479-1486
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Tidskriftsartikel (refereegranskat)abstract
- Vollaard NB, Constantin-Teodosiu D, Fredriksson K, Rooyackers O, Jansson E, Greenhaff PL, Timmons JA, Sundberg CJ. Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance. J Appl Physiol 106: 1479-1486, 2009. First published February 5, 2009; doi:10.1152/japplphysiol.91453.2008.-It has not been established which physiological processes contribute to endurance training-related changes (Delta) in aerobic performance. For example, the relationship between intramuscular metabolic responses at the intensity used during training and improved human functional capacity has not been examined in a longitudinal study. In the present study we hypothesized that improvements in aerobic capacity ((V) over dotO(2max)) and metabolic control would combine equally to explain enhanced aerobic performance. Twenty-four sedentary males (24 +/- 2 yr; 1.81 +/- 0.08 m; 76.6 +/- 11.3 kg) undertook supervised cycling training (45 min at 70% of pretraining (V) over dotO(2max)) 4 times/wk for 6 wk. Performance was determined using a 15-min cycling time trial, and muscle biopsies were taken before and after a 10-min cycle at 70% of pretraining (V) over dotO(2max) to quantify substrate metabolism. Substantial interindividual variability in training-induced adaptations was observed for most parameters, yet ""low responders"" for Delta(V) over dotO(2max) were not consistently low responders for other variables. While (V) over dotO(2max) and time trial performance were related at baseline (r(2) = 0.80, P < 0.001), the change in (V) over dotO(2max) was completely unrelated to the change in aerobic performance. The maximal parameters Delta(V) over dotE(max) and Delta Veq(max) (Delta(V) over dotE/(V) over dotO(2max)) accounted for 64% of the variance in Delta(V) over dotO(2max) (P < 0.001), whereas Delta performance was related to changes in the submaximal parameters Veq(submax) (r(2) = 0.33; P < 0.01), muscle Delta lactate (r(2) = 0.32; P < 0.01), and Delta acetyl-carnitine (r(2) = 0.29; P < 0.05). This study demonstrates that improvements in high-intensity aerobic performance in humans are not related to altered maximal oxygen transport capacity. Altered muscle metabolism may provide the link between training stimulus and improved performance, but metabolic parameters do not change in a manner that relates to aerobic capacity changes.
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| 9. |
- Winters, Maike, et al.
(författare)
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Debunking highly prevalent health misinformation using audio dramas delivered by WhatsApp : evidence from a randomised controlled trial in Sierra Leone
- 2021
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Infectious disease misinformation is widespread and poses challenges to disease control. There is limited evidence on how to effectively counter health misinformation in a community setting, particularly in low-income regions, and unsettled scientific debate about whether misinformation should be directly discussed and debunked, or implicitly countered by providing scientifically correct information.Methods The Contagious Misinformation Trial developed and tested interventions designed to counter highly prevalent infectious disease misinformation in Sierra Leone, namely the beliefs that (1) mosquitoes cause typhoid and (2) typhoid co-occurs with malaria. The information intervention for group A (n=246) explicitly discussed misinformation and explained why it was incorrect and then provided the scientifically correct information. The intervention for group B (n=245) only focused on providing correct information, without directly discussing related misinformation. Both interventions were delivered via audio dramas on WhatsApp that incorporated local cultural understandings of typhoid. Participants were randomised 1:1:1 to the intervention groups or the control group (n=245), who received two episodes about breast feeding.Results At baseline 51% believed that typhoid is caused by mosquitoes and 59% believed that typhoid and malaria always co-occur. The endline survey was completed by 91% of participants. Results from the intention-to-treat, per-protocol and as-treated analyses show that both interventions substantially reduced belief in misinformation compared with the control group. Estimates from these analyses, as well as an exploratory dose–response analysis, suggest that direct debunking may be more effective at countering misinformation. Both interventions improved people’s knowledge and self-reported behaviour around typhoid risk reduction, and yielded self-reported increases in an important preventive method, drinking treated water.Conclusion These results from a field experiment in a community setting show that highly prevalent health misinformation can be countered, and that direct, detailed debunking may be most effective.Trial registration number NCT04112680.
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