Validation of a novel approach to assess metabolic flexibility to a high-fat meal in a whole-body room calorimeter.

Abstract

Metabolic inflexibility to Western high-fat diets may contribute to the obesity epidemic. However, validated methods for assessing metabolic flexibility (MetFlex) to high-fat meals are currently lacking. The purpose of this study was to evaluate the reliability of a novel approach for determining MetFlex to a high-fat meal and to compare it with the gold standard for measuring MetFlex to high-carbohydrate loads. Eight healthy adults were enrolled in our study, which consisted of the following two assessments of MetFlex: 1) MetFlex to fat, via two overnight stays in a metabolic chamber separated by 5 to 7 days; and 2) Metflex to carbohydrates, via a two-step hyperinsulinemic-euglycemic clamp measured >5 days later. Participants were predominantly White and male, with mean (SD) age of 29.4 (6.3) years and BMI of 25.4 (4.1) kg/m². MetFlex to fat displayed satisfactory test-retest reliability (intraclass correlation coefficient > 0.70) for several outcomes but showed no correlation to MetFlex measured during the clamp. Overnight changes in substrate oxidation following a high-fat dinner meal represent a unique aspect of MetFlex that cannot be captured using more conventional methods. Our findings warrant prospective studies to determine whether these parameters are predictive of the development of obesity or metabolic dysfunction.