Bovard 2018 IOC134

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Integrative determinants of oxygen uptake and biomolecular markers of exercise training.

Link: Mitochondr Physiol Network 23.08

Bovard J, Boushel R (2018)

Event: IOC134

Physical activity is a necessity for healthy living. Essential to this is the assessment of cardiorespiratory fitness by measuring maximal oxygen uptake (VO2max), which is the one of the strongest predictors of morbidity and mortality. While classically thought to be determined by oxygen delivery to working muscle, the adaptive responses of muscle oxidative capacity and therefore mitochondrial contributions are not fully understood. Moreover, changes in VO2max with standardized training programs vary substantially. A greater understanding of this variation may be achieved by a systems biology approach characterizing the biomolecular response to exercise (“the exercise responsome”), including differences in arterial and venous concentrations of proteins and metabolites (i.e., fluxomics). Given the “drug-like” effects of molecules secreted by muscle during exercise, characterizing the exercise responsome can highlight exercise dosages that optimize circulating biomolecule levels, adaptations to training, and therefore health benefits of exercise. Thus, the purposes of this study are three-fold: (1) To understand the relative and integrated contributions of the circulatory and muscle oxidative components to oxygen uptake with exercise training; (2) to assess the “exercise responsome”; and (3) to associate determinants of oxygen uptake with biomolecular markers of health.

Trained and untrained individuals will be recruited. At Visit 1, maximal oxygen uptake and critical power will be assessed. At Visit 2, blood samples will be drawn in the morning (fasted), prior to an exhaustive bout of exercise, and at multiple post-exercise time points to assess the proteomic and metabolomic responses to exercise. Body composition will be assessed, and muscle biopsies will be taken prior to and after exercise to assess mitochondrial function and oxidative stress. Specifically, a substrate and inhibitor protocol will be applied to assess OXPHOS, substrate and coupling control, LEAK respiration, mitochondrial p50, and COX excess capacity. At Visit 3, subjects will be instrumented with femoral arterial and venous catheters, as well as antecubital venous catheterization, and complete multiple incremental exercise tests on 2-legged cycling and 1-leg knee extension ergometers. During each exercise stage, blood samples will be drawn to measure fluxomics and circulatory responses to exercise will be determined. Integrative determinants of oxygen uptake will be modeled to include muscle mass-normalized O2 delivery, mitochondrial excess capacity, relative activation of mitochondria, and the role of p50 in O2 extraction. Bioinformatic analysis of omic responses alongside integrative determinants will investigate molecular-to-organ signaling networks. Trained vs. untrained groups and males vs. females will be compared. Untrained subjects will then complete a 12-16-week exercise training program, including aerobic intervals and resistance exercise, before repeating the 3 visits. Pre- and post-training will be compared.


Bioblast editor: Plangger M O2k-Network Lab: CA Vancouver Boushel RC


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 


Organism: Human  Tissue;cell: Skeletal muscle 


Coupling state: LEAK 

HRR: Oxygraph-2k 


Affiliations

School Kinesiology, Univ British Columbia, Vancouver, Canada