Work

Multilevel metabolic adaptation to exercise training

Year: 2026

Type: article

Abstract: 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. 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. 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. 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. Many people exercise to lose weight, but results are often smaller than expected. This study explored why this happens. We studied adults with overweight who completed a 12-week supervised walking program and mice who were also regularly exercised. We measured how much energy they used each day, how their bodies used energy at rest, how active they were, and the size of key internal organs using advanced imaging. We found that body weight changed very little despite regular exercise. The body adapted by using less energy at rest, walking more efficiently, and reducing the size of highly metabolic organs such as the liver and kidneys. These changes helped conserve energy and may explain why exercise alone does not lead to major weight loss Knaan et al. examine metabolic and behavioral adaptations to a 12-week supervised aerobic exercise program in adults with overweight. Exercise induces energy compensation through reduced resting metabolism, improved movement efficiency, and selective shrinkage of highly metabolic organs, thereby limiting weight loss.

Source: Communications Medicine

DOI: 10.1038/s43856-026-01502-z