Metabolic flexibility differs by body composition in adults

BACKGROUND & AIMS With the rise of global cardiometabolic diseases, it is important to investigate risk factors such as obesity. Metabolic flexibility, the ability to maintain metabolic homeostasis following an acute challenge, can reflect cardiometabolic health. We investigated the association between body composition and the metabolic flexibility following meal consumption in an adult population. METHODS In this study of 1027 participants (mean age 44.0 y ± SD 4.2 y), we administered a mixed-macronutrient meal challenge. Fasting and 2-h postprandial plasma were assayed for lipids, glycemic, and inflammation biomarkers. We characterized metabolic flexibility through meal-induced biomarker responses (%Δ, the difference between postprandial and fasting concentrations, divided by fasting concentration). We then compared the responses by sex-specific tertiles of body mass index (BMI) and percent body fat. RESULTS With every unit (kg/m2) increase in BMI, %Δ (95% confidence interval) increased by 0.17% (0.09, 0.26%) for total cholesterol, 0.31% (0.07, 0.54%) for triglycerides, and 0.11% (0.01, 0.20%) for apoA-I, whereas insulin elevation was reduced (-6.30%; -8.41, -4.20%), and the reduction in leptin was attenuated (0.64%; 0.25, 1.05%). With each unit (percent) increase in body fat, we observed similar changes in the %Δ of total cholesterol and leptin but not in triglycerides, apoA-I, or insulin. Glucose response increased by 0.29% (0.06, 0.51%) as body fat increases by one unit. CONCLUSION Metabolic flexibility, as assessed by biomarker responses to an acute physiological meal challenge, differed by body composition. These findings may help elucidate the pathways through which obesity contributes to cardiometabolic diseases.