Different Isocaloric Meals and Adiposity Modify Energy Expenditure, Clinical and Metabolomic Biomarkers During Resting and Exercise States in a Randomized Cross-over Acute Trial of Normal Weight and Overweight/obese Men

Abstract Background Few studies have assessed the integrative effects of diet, BMI, and exercise on postprandial changes of energy and circulating metabolic profiles. Objectives We aimed to assess the collective effects of three isocaloric diets high in carbohydrate (74.2% energy), fat (64.6% energy), or protein (39.5% energy) on energy expenditure, clinical and metabolomic biomarkers under resting and exercise conditions in normal-weight and overweight/obese men. Methods This cross-over controlled acute trial included 20 normal-weight (BMI: 18.5– <24) and 20 overweight/obese (BMI ≥ 24 kg/m2) men aged 18–45 years. Each of three test meals was provided for two continuous days: “Resting Day” without exercise, followed by “Exercise Day” with a bicycling exercise of 50% maximal oxygen consumption (postprandial 90–120 min). Energy expenditure (exploratory outcome of primary interest) was measured using indirect calorimetry. Fasting and postprandial 2-hour serum clinical and metabolomic biomarkers (secondary interest) were measured. Mixed models were used to examine the effects of diet, time, and/or BMI category. Results On Resting Day, no significant between-meal differences were detected for energy expenditure. However, high-carbohydrate and high-fat meals induced the highest postprandial 2-hour increase in glucose (0.34 ± 0.15 mmol/L) and triglyceride (0.95 ± 0.09 mmol/L) respectively, while high-protein meal reduced glucose (-0.48 ± 0.08 mmol/L) and total cholesterol (-0.01 ± 0.03 mmol/L, all Pdiet < 0.001). On Exercise Day, high-carbohydrate diet significantly promoted carbohydrate oxidation rate but suppressed fat oxidation rate (Pdiet < 0.05), while its postprandial glucose response was attenuated by bicycling (-0.31 ± 0.03 mmol/L, Pexercise < 0.001). 69 metabolites were identified as key features in discriminating the three meals, and overweight/obese men had more varieties of metabolites than normal-weight men. Conclusions Three isocaloric meals induced unique postprandial changes in clinical and metabolomic biomarkers, while exercise prevented high-carbohydrate meal induced hyperglycemia. Overweight/obese men were more responsive to the meal challenges than normal-weight men. This trial was registered at clinicaltrials.gov as NCT03231618.