Menopausal duration and relative skeletal muscle index predict metabolic inflexibility during walking in postmenopausal women with overweight/obesity

Menopause predisposes a diminished capacity to alter oxidative substrate during exercise-a risk factor for cardiometabolic diseases (CMDs). Since walking behavior influences CMD, identifying factors associated with substrate use during walking may inform strategies to attenuate risk. This study assessed changes in lipid (ΔFATox) and carbohydrate (ΔCHOox) oxidation during walking and identified physiological predictors. Thirty-six women [64 ± 7 yr; body mass index (BMI): 29.5 ± 4.9 kg/m²] completed a treadmill task (0.9 m/s, 0% grade) with indirect calorimetry to quantify oxygen uptake (V̇o₂) kinetics, ΔFATox, and ΔCHOox. Exercise capacity was assessed via a 6-min walk test. Body composition, including relative skeletal muscle index (RSMI), was assessed using dual-energy X-ray absorptiometry. ΔFATox was correlated with age (r = -0.465, P = 0.004), menopausal duration (rs = -0.478, P = 0.004), BMI (rs = 0.398, P = 0.028), RSMI (r = 0.531, P = 0.001), and excessive postexercise V̇o₂ (rs = 0.430, P = 0.009). ΔCHOox was correlated with O₂ deficit (rs = 0.500, P = 0.002). Menopausal duration, RSMI, and recovery V̇o₂ mean response time explained the most variance in ΔFATox (adjusted r² = 0.534, P < 0.001). Menopausal duration, visceral adipose tissue mass, and O₂ deficit explained the most variance in ΔCHOox (adjusted r² = 0.371, P < 0.001). Age and menopausal duration were associated with reduced ΔFATox during walking. Menopausal duration was the strongest exploratory predictor of metabolic inflexibility. RSMI outperformed exercise capacity and V̇o₂ uptake kinetics in predicting ΔFATox during walking.NEW & NOTEWORTHY Changes in metabolic inflexibility were detected during walking at intensities reflecting activities of independent living in sedentary postmenopausal women with overweight/obesity. This work provides evidence for a stronger link between menopausal duration and metabolic inflexibility during walking when compared with chronological age. Our analyses also revealed that RSMI was a key predictor ΔFATox during walking and thus identified it as a clinically relevant, modifiable target for the improvement of cardiometabolic health in future clinical trials.