Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/20887
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dc.contributor.authorLessard, Sarah Jen_UK
dc.contributor.authorRivas, Donato Aen_UK
dc.contributor.authorAlves-Wagner, Ana Ben_UK
dc.contributor.authorHirshman, Michael Fen_UK
dc.contributor.authorGallagher, Iain Jen_UK
dc.contributor.authorConstantin-Teodosiu, Dumitruen_UK
dc.contributor.authorAtkins, Ryanen_UK
dc.contributor.authorGreenhaff, Paul Len_UK
dc.contributor.authorQi, Nathan Ren_UK
dc.contributor.authorGustafsson, Thomasen_UK
dc.contributor.authorFielding, Roger Aen_UK
dc.contributor.authorTimmons, James Aen_UK
dc.contributor.authorBritton, Steven Len_UK
dc.contributor.authorKoch, Lauren Gen_UK
dc.contributor.authorGoodyear, Laurie Jen_UK
dc.date.accessioned2016-10-08T22:56:50Z-
dc.date.available2016-10-08T22:56:50Zen_UK
dc.date.issued2013-08en_UK
dc.identifier.urihttp://hdl.handle.net/1893/20887-
dc.description.abstractLow aerobic exercise capacity is a risk factor for diabetes and a strong predictor of mortality, yet some individuals are "exercise-resistant" and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease risk, we used selective breeding for 15 generations to develop rat models of low and high aerobic response to training. Before exercise training, rats selected as low and high responders had similar exercise capacities. However, after 8 weeks of treadmill training, low responders failed to improve their exercise capacity, whereas high responders improved by 54%. Remarkably, low responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise-resistant phenotype segregates with disease risk. Low responders had impaired exercise-induced angiogenesis in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low responders. Low responders had increased stress/inflammatory signaling and altered transforming growth factor-β signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system, we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease.en_UK
dc.language.isoenen_UK
dc.publisherAmerican Diabetes Associationen_UK
dc.relationLessard SJ, Rivas DA, Alves-Wagner AB, Hirshman MF, Gallagher IJ, Constantin-Teodosiu D, Atkins R, Greenhaff PL, Qi NR, Gustafsson T, Fielding RA, Timmons JA, Britton SL, Koch LG & Goodyear LJ (2013) Resistance to aerobic exercise training causes metabolic dysfunction and reveals novel exercise-regulated signaling networks. Diabetes, 62 (8), pp. 2717-2727. https://doi.org/10.2337/db13-0062en_UK
dc.rightsThe publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study.en_UK
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_UK
dc.titleResistance to aerobic exercise training causes metabolic dysfunction and reveals novel exercise-regulated signaling networksen_UK
dc.typeJournal Articleen_UK
dc.rights.embargodate3000-01-01en_UK
dc.rights.embargoreason[Diabetes 2013.pdf] The publisher does not allow this work to be made publicly available in this Repository therefore there is an embargo on the full text of the work.en_UK
dc.identifier.doi10.2337/db13-0062en_UK
dc.citation.jtitleDiabetesen_UK
dc.citation.issn1939-327Xen_UK
dc.citation.issn0012-1797en_UK
dc.citation.volume62en_UK
dc.citation.issue8en_UK
dc.citation.spage2717en_UK
dc.citation.epage2727en_UK
dc.citation.publicationstatusPublisheden_UK
dc.citation.peerreviewedRefereeden_UK
dc.type.statusVoR - Version of Recorden_UK
dc.author.emaili.j.gallagher@stir.ac.uken_UK
dc.contributor.affiliationJoslin Diabetes Centeren_UK
dc.contributor.affiliationTufts Universityen_UK
dc.contributor.affiliationJoslin Diabetes Centeren_UK
dc.contributor.affiliationJoslin Diabetes Centeren_UK
dc.contributor.affiliationSporten_UK
dc.contributor.affiliationUniversity of Nottinghamen_UK
dc.contributor.affiliationUniversity of Nottinghamen_UK
dc.contributor.affiliationUniversity of Nottinghamen_UK
dc.contributor.affiliationUniversity of Michiganen_UK
dc.contributor.affiliationKarolinska University Hospitalen_UK
dc.contributor.affiliationTufts Universityen_UK
dc.contributor.affiliationLoughborough Universityen_UK
dc.contributor.affiliationUniversity of Michiganen_UK
dc.contributor.affiliationUniversity of Michiganen_UK
dc.contributor.affiliationJoslin Diabetes Centeren_UK
dc.identifier.isiWOS:000322431100017en_UK
dc.identifier.scopusid2-s2.0-84891687846en_UK
dc.identifier.wtid629335en_UK
dc.contributor.orcid0000-0002-8630-7235en_UK
dcterms.dateAccepted2013-08-31en_UK
dc.date.filedepositdate2014-08-13en_UK
rioxxterms.typeJournal Article/Reviewen_UK
rioxxterms.versionVoRen_UK
local.rioxx.authorLessard, Sarah J|en_UK
local.rioxx.authorRivas, Donato A|en_UK
local.rioxx.authorAlves-Wagner, Ana B|en_UK
local.rioxx.authorHirshman, Michael F|en_UK
local.rioxx.authorGallagher, Iain J|0000-0002-8630-7235en_UK
local.rioxx.authorConstantin-Teodosiu, Dumitru|en_UK
local.rioxx.authorAtkins, Ryan|en_UK
local.rioxx.authorGreenhaff, Paul L|en_UK
local.rioxx.authorQi, Nathan R|en_UK
local.rioxx.authorGustafsson, Thomas|en_UK
local.rioxx.authorFielding, Roger A|en_UK
local.rioxx.authorTimmons, James A|en_UK
local.rioxx.authorBritton, Steven L|en_UK
local.rioxx.authorKoch, Lauren G|en_UK
local.rioxx.authorGoodyear, Laurie J|en_UK
local.rioxx.projectInternal Project|University of Stirling|https://isni.org/isni/0000000122484331en_UK
local.rioxx.freetoreaddate3000-01-01en_UK
local.rioxx.licencehttp://www.rioxx.net/licenses/under-embargo-all-rights-reserved||en_UK
local.rioxx.filenameDiabetes 2013.pdfen_UK
local.rioxx.filecount1en_UK
local.rioxx.source0012-1797en_UK
Appears in Collections:Faculty of Health Sciences and Sport Journal Articles

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