Assessing metabolic flexibility in adults under physiological conditions: Effects of dietary fat and exercise in whole‐room calorimetry

Abstract

Metabolic flexibility (MetaFlex) reflects the ability to adjust substrate oxidation to changes in fuel availability and energy demand. How MetaFlex should be assessed under physiologically relevant metabolic challenges remains unclear. Data from two studies were analyzed in adults with contrasting adiposity and training status, known to influence MetaFlex: healthy lean inactive or trained adults (Ln‐inactive/Ln‐trained, BMI: 19–25 kg/m ² ), inactive adults with obesity (Ob‐Inactive, BMI: 30–40 kg/m ² ), and weight‐reduced inactive or trained (RO‐inactive/RO‐trained, BMI: 25‐40 kg/m ² , >10% weight loss). Participants completed 24‐h stays in a whole‐room calorimeter under a low‐fat (20% fat, LF‐EB), high‐fat (50% fat, HF‐EB) diet, or acute moderate‐intensity exercise (EX‐EB) in energy balance, or resting in energy balance (REST‐EB), or acute exercise inducing 15% energy deficit (EX‐ED). MetaFlex was assessed using day‐night respiratory quotient (ΔRQ _day‐night ), nighttime RQ (RQ _sleep ) and 24‐h variances of RQ and insulin. Linear mixed models were used. Compared with LF‐EB, HF‐EB increased ΔRQ (Difference LSMeans ± SE, 0.040 ± 0.016, p  = 0.02) and 24‐h RQ variance (0.895 ± 0.345, p  = 0.02) and reduced 24‐h insulin variance (0.65 ± 0.13, p  < 0.001) across groups. EX‐EB did not modify any MetaFlex index. During EX‐ED, 24‐h insulin variance differed by group, with higher values in Ob‐Inactive compared with Ln‐Inactive, RO‐Trained, and RO‐Inactive ( p  < 0.022 for all). MetaFlex is challenge‐dependent. When EB is maintained, short‐term high‐fat feeding is more effective than acute exercise for probing MetaFlex. Exercise combined with an energy deficit reveals between‐group differences driven primarily by insulin dynamics. Individuals with obesity display reduced MetaFlex, whereas weight loss—especially when combined with training—partially restores MetaFlex.