This study investigated the relationships between physical activity behaviors and energy metabolism in 64 middle-aged, sedentary adults with metabolic syndrome. Associations were examined cross-sectionally, and a 6-month randomized controlled trial was conducted to investigate whether reducing daily sedentary time through increased standing and light-to-moderate-intensity physical activity, without adding intentional exercise training, could improve metabolic health.

The time spent in activity behaviors was measured with hip-worn accelerometers continuously for 6 months. Cardiorespiratory fitness was determined with maximal cycle ergometry. Metabolic outcomes were assessed at baseline, 3 months, and 6 months using hyperinsulinemic euglycemic clamp, positron emission tomography, indirect calorimetry, fasting blood samples, body composition, and anthropometrics.

Activity behaviors and fitness associated with whole-body and skeletal muscle insulin sensitivity, but only associations between standing and insulin sensitivity markers were independent of adiposity. Sedentary time associated adversely and standing and physical activity, of even light-intensity, beneficially with lipid metabolism and metabolic flexibility. A 50-min reduction in daily sedentary time attenuated increases in several cardiometabolic markers at 3 months, but the intervention did not improve metabolic flexibility in 6 months. However, additional analyses showed that successfully reducing daily sedentary time by 30 min or more improved metabolic flexibility compared to continued high sedentary time.
Improvements in metabolic flexibility also correlated with increased standing time.

The findings highlight the importance of a healthy body composition and suggest that reducing sedentary time and increasing standing and light-intensity activity might help slow down the progression of metabolic diseases in inactive individuals with an increased cardiometabolic risk.