Whole-Room Indirect Calorimetry in the Study of Obesity, Insulin Resistance and Metabolic Flexibility: A Narrative Review.

Obesity and insulin resistance are characterized by substantial heterogeneity in energy expenditure and substrate utilization. Whole-room indirect calorimetry (WRIC) enables continuous assessment of oxygen consumption, carbon dioxide production, energy expenditure, respiratory exchange ratio (RER), and substrate oxidation under controlled conditions. This narrative review examines the physiological interpretation, methodological strengths, limitations, and applications of WRIC in obesity, insulin resistance, metabolic flexibility, and weight-loss interventions. By enabling prolonged observation during resting, postprandial, exercise, and sleep periods, WRIC complements short-term indirect calorimetry and free-living energy expenditure measurements obtained using doubly labeled water. Validation studies generally demonstrate high technical accuracy and reproducibility for respiratory gas exchange and 24 h energy expenditure measured using WRIC. In contrast, estimates of the thermic effect of food, short-term changes in RER, and substrate oxidation are more sensitive to protocol design, energy balance, physical activity, and analytical procedures. Available studies demonstrate substantial interindividual variability rather than a uniform metabolic pattern associated with obesity or insulin resistance. Direct WRIC evidence concerning contemporary anti-obesity pharmacotherapy and metabolic and bariatric surgery remains limited. Standardized protocols and complementary assessments of body composition, insulin sensitivity, and free-living energy expenditure are needed to improve the comparability and interpretation of findings across studies.