Oral Presentation ANZOS-OSSANZ-AOCO Joint Annual Scientific Meeting 2017

Metabolic flexibility drives energy expenditure (#21)

Steven Smith 1
  1. Translational Research Institute for Metabolism and Diabetes, Orlando, FLORIDA, United States

Metabolic flexibility, defined as an ability to switch oxidation between carbohydrate and fatty acids declines as body fatness increases.  This is known as metabolic inflexibility.  This is due in part to a decrease in insulin stimulated glucose oxidation after a meal but also a decline in fatty acid oxidation in the post-absorptive state.  Metabolic flexibility improves with weight loss, exercise training, and certain pharmacological treatments.

In parallel, dynamical systems modeling has provided new insights that relatively small changes in energy expenditure accumulate to produce fat gain or loss. These changes, on the order of 50-100kcal / day are difficult to measure in free living humans.  Recent technical and procedural advances in the application of high resolution indirect calorimetry now allow us to measure very small changes in substrate utilization and energy expenditure.

We will review recent work demonstrating that switching fuel supply from carbohydrates to fat increases energy expenditure in humans. This thermogenesis has been observed not only with large changes in fatty acid supply (i.e. IntralipidTM infusion and ketogenic diets) but also under pharmacological conditions where small changes in metabolic flexibility produce meaningful changes in nocturnal energy expenditure.  In addition, preliminary data suggests that this effect plays a role in the early responses to calorie restriction / weight loss. 

These early results are pushing us to devise new approaches to the treatment of obesity by enhancing metabolic flexibility and therefore nocturnal thermogenesis; however, the real value may be in the crafting of population level strategies to prevent weight gain.