KOCH, Lauren G.; BRITTON, Steven L.; Medical College of Ohio: Metabolic Syndrome X emerges from selection for intrinsic aerobic running capacity in rats

Development of an oxygen atmosphere widened the redox potential for energy transfer that was presumably permissive for the co-evolution of biological complexity in the form of multicellular organisms. From this we hypothesized that variation in oxygen utilization pathways must be central to a large part of our biology and thus also define the continuum between health and disease. If this hypothesis is valid, we reasoned that divergent artificial selection for aerobic capacity would concurrently produce lines that differ for health status. We thus began selective breeding for the intrinsic (i.e., untrained) capacity to perform an aerobic treadmill run in rats to create lines of Low Capacity Runners (LCR) and High Capacity Runners (HCR). Selection was based upon distance run to exhaustion using a speed-ramped protocol. By eleven generations of selection the HCR were superior to the LCR for distance run to exhaustion (347%) and VO2max (60%). Each line was assessed for a battery of measures that included cardiovascular function, glucose metabolism, blood lipid levels, and efficiency of oxygen utilization. The LCR and HCR appear to have diverged for these measures in a fashion that emulates metabolic syndrome x. These models may provide general substrate for defining the pivotal role oxygen has in health and disease at all levels of biological organization. Supported by NIH (HL 64270 and RR 17718).