Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/20887
Appears in Collections:Faculty of Health Sciences and Sport Journal Articles
Peer Review Status: Refereed
Title: Resistance to aerobic exercise training causes metabolic dysfunction and reveals novel exercise-regulated signaling networks
Authors: Lessard, Sarah J
Rivas, Donato A
Alves-Wagner, Ana B
Hirshman, Michael F
Gallagher, Iain J
Constantin-Teodosiu, Dumitru
Atkins, Ryan
Greenhaff, Paul L
Qi, Nathan R
Gustafsson, Thomas
Fielding, Roger A
Timmons, James A
Britton, Steven L
Koch, Lauren G
Goodyear, Laurie J
Contact Email: i.j.gallagher@stir.ac.uk
Issue Date: Aug-2013
Publisher: American Diabetes Association
Citation: Lessard 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.
Abstract: Low 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.
Type: Journal Article
URI: http://hdl.handle.net/1893/20887
DOI Link: http://dx.doi.org/10.2337/db13-0062
Rights: The 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.
Affiliation: Joslin Diabetes Center
Tufts University
Joslin Diabetes Center
Joslin Diabetes Center
Sport
University of Nottingham
University of Nottingham
University of Nottingham
University of Michigan
Karolinska University Hospital
Tufts University
Loughborough University
University of Michigan
University of Michigan
Joslin Diabetes Center

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