Using Dynamic Metabolic Adjustments During Exercise to Quantify Metabolic Flexibility
Authors: Flores Phillip H. , Rodriguez Jorge , Yang Jeremy , Cotter Joshua A. , Harris Michael B. 
Published: April 2020

Metabolic flexibility is a broad concept referring to how an organism responds to changing energy demands. Metabolic demands are met with a combination of protein, carbohydrate (CHO) and fatty acid (FA) fuels. Metabolic flexibility reflects the dynamic capacity to adjust proportionate recruitment of fuel types to efficiently match metabolic demands. Poor metabolic flexibility is associated with impaired capacity to efficiently recruit FA as a metabolic fuel and the development of severe and debilitating diseases. Much interest is focused on improving metabolic flexibility to prevent and treat metabolic diseases. Lacking, however, is an easily quantifiable index of metabolic flexibility. Exercise intensity influences both metabolic rate as well as recruitment of CHO and FA fuels. Dynamic patterns of fuel selection during the onset of sustained low to moderate intensity exercise (SLMIE), therefore, reflect capacities for metabolic flexibility. At the onset of SLMIE, increased metabolic demands are initially satisfied by increasing CHO metabolism. Subsequently, a healthy and flexible metabolism will adjust fuel choice to increase proportionate FA metabolism. Reduced metabolic flexibility resists the recruitment of FA fuels and compromises this dynamic adjustment. It is proposed that metabolic responses to SLMIE can provide an index of metabolic flexibility.Oxygen consumption and CO2 production in healthy male and female subjects were measured before and during a period of SLMIE (50% VO2 max) using a cycle ergometer. Body composition was assessed using dual energy X‐ray absorptiometry (DXA). The Respiratory Exchange Ratio (RER) was used to illustrate relative proportions of CHO and FA oxidation and track the dynamic changes in RER during exercise to identify the latency to a metabolic adjustment favoring FA metabolism as an indicator of metabolic flexibility. We test the hypotheses that this metabolic adjustment latency indicator will be resolved with this protocol, and that it will correlate with body composition characteristics associated with metabolic flexibility and metabolic health.Subjects presented patterns of RER illustrating increasing CHO metabolism at the onset of exercise and subsequent increases in proportionate FA metabolism, initiating within 10 to 25 minutes of sustained exercise. Latencies to this metabolic adjustment differed between subjects. A preliminary analysis suggests that subjects fell into two categories, with metabolic adjustment occurring between 10–15 minutes or between 22 and 28 minutes of the onset of exercise. On average, subjects within the longer metabolic adjustment latency subset had greater visceral adipose tissue (VAT) mass, greater VAT mass as a proportion of body weight, lower regionalization of adipose tissue in the gynoid region, and greater android‐gynoid percent fat ratio in body fat distribution. Subject testing is ongoing, however, preliminary results illustrate that metabolic adjustment latencies can be resolved, and that short latencies may correlate with body composition characteristics also associated with metabolic flexibility and metabolic health.Support or Funding InformationCSULB institutional award, and NIH awards 1R15HL126105, 1SC2GM112570, UL1GM118979, TL4GM118980, and RL5GM118978.