Impaired metabolic flexibility to fasting is associated with increased ad libitum energy intake in healthy adults

• Published in: Obesity (Silver Spring, Md.) Vol. 32; no. 5; p. 949
• Main Authors: Unlu, Yigit, Piaggi, Paolo, Stinson, Emma J, Cabeza De Baca, Tomás, Rodzevik, Theresa L, Walter, Mary, Krakoff, Jonathan, Chang, Douglas C
• Format: Journal Article
• Language: English
• Published: United States 01.05.2024
• Subjects: Adult; Body Mass Index; Dietary Carbohydrates - administration & dosage; Dietary Carbohydrates - metabolism; Eating - physiology; Energy Intake; Energy Metabolism - physiology; Fasting; Female; Healthy Volunteers; Humans; Lipid Metabolism - physiology; Male; Middle Aged; Oxidation-Reduction
• ISSN: 1930-739X
• DOI: 10.1002/oby.24011

We investigated how changes in 24-h respiratory exchange ratio (RER) and substrate oxidation during fasting versus an energy balance condition influence subsequent ad libitum food intake. Forty-four healthy, weight-stable volunteers (30 male and 14 female; mean [SD], age 39.3 [11.0] years; BMI 31.7 [8.3] kg/m ) underwent 24-h energy expenditure measurements in a respiratory chamber during energy balance (50% carbohydrate, 30% fat, and 20% protein) and 24-h fasting. Immediately after each chamber stay, participants were allowed 24-h ad libitum food intake from computerized vending machines. Twenty-four-hour RER decreased by 9.4% (95% CI: -10.4% to -8.5%; p < 0.0001) during fasting compared to energy balance, reflecting a decrease in carbohydrate oxidation (mean [SD], -2.6 [0.8] MJ/day; p < 0.0001) and an increase in lipid oxidation (2.3 [0.9] MJ/day; p < 0.0001). Changes in 24-h RER and carbohydrate oxidation in response to fasting were correlated with the subsequent energy intake such that smaller decreases in fasting 24-h RER and carbohydrate oxidation, but not lipid oxidation, were associated with greater energy intake after fasting (r = 0.31, p = 0.04; r = 0.40, p = 0.007; and r = -0.27, p = 0.07, respectively). Impaired metabolic flexibility to fasting, reflected by an inability to transition away from carbohydrate oxidation, is linked with increased energy intake.