An expanded repertoire of intensity-dependent exercise-responsive plasma proteins tied to loci of human disease risk.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 07 2020
02 07 2020
Historique:
received:
01
02
2020
accepted:
10
06
2020
entrez:
4
7
2020
pubmed:
4
7
2020
medline:
10
2
2021
Statut:
epublish
Résumé
Routine endurance exercise confers numerous health benefits, and high intensity exercise may accelerate and magnify many of these benefits. To date, explanatory molecular mechanisms and the influence of exercise intensity remain poorly understood. Circulating factors are hypothesized to transduce some of the systemic effects of exercise. We sought to examine the role of exercise and exercise intensity on the human plasma proteome. We employed an aptamer-based method to examine 1,305 plasma proteins in 12 participants before and after exercise at two physiologically defined intensities (moderate and high) to determine the proteomic response. We demonstrate that the human plasma proteome is responsive to acute exercise in an intensity-dependent manner with enrichment analysis suggesting functional biological differences between the moderate and high intensity doses. Through integration of available genetic data, we estimate the effects of acute exercise on exercise-associated traits and find proteomic responses that may contribute to observed clinical effects on coronary artery disease and blood pressure regulation. In sum, we provide supportive evidence that moderate and high intensity exercise elicit different signaling responses, that exercise may act in part non-cell autonomously through circulating plasma proteins, and that plasma protein dynamics can simulate some the beneficial and adverse effects of acute exercise.
Identifiants
pubmed: 32616758
doi: 10.1038/s41598-020-67669-0
pii: 10.1038/s41598-020-67669-0
pmc: PMC7331669
doi:
Substances chimiques
Blood Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10831Subventions
Organisme : NIH HHS
ID : R01AG061034
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 16SFRN31720000
Pays : United States
Organisme : NIH HHS
ID : R01 HL125869
Pays : United States
Organisme : NIH HHS
ID : HL007208
Pays : United States
Références
Gomez-Pinilla, F. & Hillman, C. The influence of exercise on cognitive abilities. Compr. Physiol. 3(1), 403–428 (2013).
pubmed: 23720292
pmcid: 3951958
Leon, A. S., Connett, J., Jacobs, D. R. Jr. & Rauramaa, R. Leisure-time physical activity levels and risk of coronary heart disease and death. The multiple risk factor intervention trial. JAMA 258(17), 2388–2395 (1987).
pubmed: 3669210
Cormie, P., Zopf, E. M., Zhang, X. & Schmitz, K. H. The impact of exercise on cancer mortality, recurrence, and treatment-related adverse effects. Epidemiol. Rev. 39(1), 71–92 (2017).
pubmed: 28453622
Kujala, U. M., Kaprio, J., Sarna, S. & Koskenvuo, M. Relationship of leisure-time physical activity and mortality: The Finnish twin cohort. JAMA 279(6), 440–444 (1998).
pubmed: 9466636
Mora, S., Cook, N., Buring, J. E., Ridker, P. M. & Lee, I. M. Physical activity and reduced risk of cardiovascular events: Potential mediating mechanisms. Circulation 116(19), 2110–2118 (2007).
pubmed: 17967770
pmcid: 2117381
Eckel, R. H. et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129(25 Suppl 2), S76-99 (2014).
pubmed: 24222015
Piercy, K. L. et al. The physical activity guidelines for Americans. JAMA 20, 20 (2018).
Petersen, R. C. et al. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 90(3), 126–135 (2018).
pubmed: 29282327
pmcid: 5772157
Swain, D. P. & Franklin, B. A. Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise. Am. J. Cardiol. 97(1), 141–147 (2006).
pubmed: 16377300
Goodman, J. M., Burr, J. F., Banks, L. & Thomas, S. G. The acute risks of exercise in apparently healthy adults and relevance for prevention of cardiovascular events. Can. J. Cardiol. 32(4), 523–532 (2016).
pubmed: 27017149
Guasch, E. et al. Atrial fibrillation promotion by endurance exercise: Demonstration and mechanistic exploration in an animal model. J. Am. Coll. Cardiol. 62(1), 68–77 (2013).
pubmed: 23583240
Neufer, P. D. et al. Understanding the cellular and molecular mechanisms of physical activity-induced health benefits. Cell. Metab. 22(1), 4–11 (2015).
pubmed: 26073496
Neilan, T. G. et al. Persistent and reversible cardiac dysfunction among amateur marathon runners. Eur. Heart. J. 27(9), 1079–1084 (2006).
pubmed: 16554314
Barres, R. et al. Acute exercise remodels promoter methylation in human skeletal muscle. Cell. Metab. 15(3), 405–411 (2012).
pubmed: 22405075
Lewis, G. D. et al. Metabolic signatures of exercise in human plasma. Sci. Transl. Med. 2(33), 33ra7 (2010).
Ramos, A. E. et al. Specific circulating microRNAs display dose-dependent responses to variable intensity and duration of endurance exercise. Am. J. Physiol. Heart Circ. Physiol. 315(2), H273–H283 (2018).
pubmed: 29600898
pmcid: 6139619
Schild, M. et al. Basal and exercise induced label-free quantitative protein profiling of m. vastus lateralis in trained and untrained individuals. J. Proteom. 122, 119–132 (2015).
Ferreira, R. et al. Unraveling the exercise-related proteome signature in heart. Basic Res. Cardiol. 110(1), 454 (2015).
pubmed: 25475830
Whitham, M. & Febbraio, M. A. The ever-expanding myokinome: Discovery challenges and therapeutic implications. Nat. Rev. Drug Discov. 15(10), 719–729 (2016).
pubmed: 27616294
Whitham, M. et al. Extracellular vesicles provide a means for tissue crosstalk during exercise. Cell. Metab. 27(1), 237–251 (2018).
pubmed: 29320704
Emilsson, V. et al. Co-regulatory networks of human serum proteins link genetics to disease. Science 361(6404), 769–773 (2018).
pubmed: 30072576
pmcid: 6190714
Sun, B. B. et al. Genomic atlas of the human plasma proteome. Nature 558(7708), 73–79 (2018).
pubmed: 29875488
pmcid: 6697541
Davies, C. T. & Few, J. D. Effects of exercise on adrenocortical function. J. Appl. Physiol. 35(6), 887–891 (1973).
pubmed: 4765828
Moreira, L. D. et al. Physical exercise and osteoporosis: Effects of different types of exercises on bone and physical function of postmenopausal women. Arq. Bras. Endocrinol. Metabol. 58(5), 514–522 (2014).
pubmed: 25166042
Kraus, W. E. et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N. Engl. J. Med. 347(19), 1483–1492 (2002).
pubmed: 12421890
Morgan, J. A., Corrigan, F. & Baune, B. T. Effects of physical exercise on central nervous system functions: A review of brain region specific adaptations. J. Mol. Psychiatry. 3(1), 3 (2015).
pubmed: 26064521
pmcid: 4461979
Daneman, R. et al. Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis. Proc. Natl. Acad. Sci. USA 106(2), 641–646 (2009).
pubmed: 19129494
Lie, D. C. et al. Wnt signalling regulates adult hippocampal neurogenesis. Nature 437(7063), 1370–1375 (2005).
pubmed: 16251967
Tharmaratnam, T., Civitarese, R. A., Tabobondung, T. & Tabobondung, T. A. Exercise becomes brain: Sustained aerobic exercise enhances hippocampal neurogenesis. J. Physiol. 595(1), 7–8 (2017).
pubmed: 28035680
Szuhany, K. L., Bugatti, M. & Otto, M. W. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J. Psychiatr. Res. 60, 56–64 (2015).
pubmed: 25455510
Fenesi, B. et al. Physical exercise moderates the relationship of apolipoprotein E (APOE) genotype and dementia risk: A population-based study. J. Alzheimers Dis. 56(1), 297–303 (2017).
pubmed: 27911292
Khera, A. V. et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat. Genet. 50(9), 1219–1224 (2018).
pubmed: 30104762
pmcid: 6128408
Thompson, P. D., Funk, E. J., Carleton, R. A. & Sturner, W. Q. Incidence of death during jogging in Rhode Island from 1975 through 1980. JAMA 247(18), 2535–2538 (1982).
pubmed: 6978411
Thompson, P. D. et al. Exercise and acute cardiovascular events placing the risks into perspective: A scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism and the Council on Clinical Cardiology. Circulation 115(17), 2358–2368 (2007).
pubmed: 17468391
Siscovick, D. S., Weiss, N. S., Fletcher, R. H. & Lasky, T. The incidence of primary cardiac arrest during vigorous exercise. N. Engl. J. Med. 311(14), 874–877 (1984).
pubmed: 6472399
Rognmo, O. et al. Cardiovascular risk of high- versus moderate-intensity aerobic exercise in coronary heart disease patients. Circulation 126(12), 1436–1440 (2012).
pubmed: 22879367
Hill, L. Arterial pressure in man while sleeping, resting, working, and bathing. J. Physiol. Lond. 22, xxvi–xxix (1897).
Cornelissen, V. A. & Smart, N. A. Exercise training for blood pressure: A systematic review and meta-analysis. J. Am. Heart Assoc. 2(1), e004473 (2013).
pubmed: 23525435
pmcid: 3603230
Consortium GT. The genotype-tissue expression (GTEx) project. Nat. Genet. 45(6), 580–585 (2013).
Mi, H., Muruganujan, A., Ebert, D., Huang, X. & Thomas, P. D. PANTHER version 14: More genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res. 47(D1), D419–D426 (2018).
pmcid: 6323939
Mi, H. & Thomas, P. In Protein Networks and Pathway Analysis (eds Nikolsky, Y. & Bryant, J.) 123–140 (Humana Press, Totowa, 2009).
Staley, J. R. et al. PhenoScanner: A database of human genotype–phenotype associations. Bioinformatics 32(20), 3207–3209 (2016).
pubmed: 27318201
pmcid: 5048068
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43(7), e47 (2015).
pubmed: 25605792
pmcid: 4402510
Benjamini, Y. & Hochberg. Y. Controlling The False Discovery Rate—A Practical And Powerful Approach to Multiple Testing. 1995.