Multilevel metabolic adaptation to exercise training

Abstract Background Exercise training often produces less weight loss than expected, a phenomenon termed exercise-induced energy compensation, but the underlying mechanisms remain unclear. This study aimed to quantify metabolic and behavioral compensation to aerobic exercise training. Methods Sixteen sedentary adults with overweight completed a 12-week supervised aerobic walking intervention targeting an energy expenditure of 20 kcal/kg/week. Total daily energy expenditure was measured using doubly labeled water, and whole-room calorimetry was used to assess changes in resting and sleeping metabolic rate (RMR, SMR) and diet-induced thermogenesis (DIT). Volumes of highly metabolic organs were quantified by magnetic resonance imaging. Physical activity was monitored objectively, walking economy was assessed during standardized treadmill walking, and dietary intake was evaluated using self-report and intake-balance methods. A parallel mouse exercise model was used to explore tissue-level adaptations. Results Exercise training induces substantial energy compensation, resulting in minimal body weight loss despite improved body composition. Total daily energy expenditure increases, while RMR and SMR decrease, accounting for most of the compensatory response. Liver and kidney volumes decrease by 5%, while brain volume remains unchanged. Exercise improves walking economy and leads to smaller-than-expected increases in daily moderate-to-vigorous physical activity. Dietary intake and DIT remain unchanged. In mice, exercise is associated with increased cellular density and mitochondrial content in the liver, indicating structural and metabolic remodeling. Conclusions Aerobic exercise training engages compensatory physiological and behavioral mechanisms that constrain energy expenditure. Reductions in basal metabolism, improved movement efficiency, and selective remodeling of metabolically active organs may collectively limit exercise-induced weight loss.