A Novel Assessment of Metabolic Flexibility: Dynamic Metabolic Adjustments to Exercise

Abstract

Metabolic flexibility is a broad concept, considering how an organism responds to changing energy demands. Increasing body fat is a significant marker and risk factor for the development of severe and debilitating diseases such as obesity, metabolic syndrome, diabetes and cardiovascular disease. Such pathologies are attributed, in part, to reduced metabolic flexibility and impaired capacity to efficiently recruit fatty acids as a metabolic fuel. Much interest is focused on improving metabolic flexibility to prevent and treat metabolic diseases. Lacking, however, is a quantifiable index of metabolic flexibility. It is well understood that exercise intensity normally influences both metabolic rate as well as the relative proportions of carbohydrate (CBH) and fatty acid (FA) fuels satisfying metabolic demands. More enigmatic are the dynamic patterns of fuel selection during the onset of exercise. We are proposing a new method to assess metabolic flexibility; quantification of latencies to metabolic adjustment favoring FA metabolism during sustained low to moderate intensity exercise. This quantification is based on measurements of Oxygen consumption and CO2 production, and calculations of Respiratory Exchange Ratio (RER) illustrating the relative proportions of CBH and FA use as metabolic fuels. At rest, metabolic demands are met with a combination of CBH and FA fuels. At the onset of exercise, increased metabolic demand is initially satisfied by increasing CBH metabolism. With sustained moderate intensity exercise, a healthy and flexible metabolism will adjust fuel choice to increase proportionate FA metabolism. We track the dynamic changes in RER during the onset of exercise, to identify the latency to this metabolic adjustment favoring FA metabolism. We propose that a healthy and flexible metabolism will adjust to the metabolic demands of exercise by efficiently adjusting fuel selection between CBH and FA. In contrast, poor metabolic flexibility will result in a longer latency to, or an absence of, this metabolic adjustment. We present measurements of RER changes during exercise to illustrate the latency of metabolic adjustment, and compare these latencies between subjects across a range of morphometric characteristics. We propose that latency to metabolic adjustment with moderate sustained intensity exercise may be a quantifiable index of metabolic flexibility. This index could assist in evaluating metabolic health, and interventions directed at preventing and treating metabolic disease.Support or Funding InformationWork reported in this publication was supported by the National Heart Lung and Blood Institute and National Institute of General Medical Sciences of the National Institutes of Health under Award Numbers 1R15HL126105, 1SC2GM112570, and by an internal award from California State University Long Beach Office of Research and Sponsored Programs. The work is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health or any other funding body.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.