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

J Nutr. 2022 Apr 1;152(4):1118-1129. doi: 10.1093/jn/nxac006.


Background: Few studies have assessed the integrative effects of diet, BMI, and exercise on postprandial changes in energy and circulating metabolic profiles.

Objectives: We aimed to assess the collective effects of 3 isocaloric meals high in carbohydrate (74.2% energy), fat (64.6% energy), or protein (39.5% energy) on energy expenditure and clinical and metabolomic biomarkers under resting and exercise conditions in normal-weight and overweight/obese men.

Methods: This crossover controlled acute trial included 20 normal-weight (BMI, 18.5 to <24 kg/m2) and 20 overweight/obese (BMI ≥24 kg/m2) men aged 18-45 years. Each of 3 test meals was provided for 2 continuous days: a resting day without exercise, followed by an exercise day with a bicycling exercise of 50% maximal oxygen consumption (postprandial 90-120 minutes). 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 meal, time, and/or BMI category.

Results: On the 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 the high-protein meal reduced glucose (-0.48 ± 0.08 mmol/L) and total cholesterol (-0.01 ± 0.03 mmol/L; all Pmeal values < 0.001). On the exercise day, a high-carbohydrate meal significantly promoted the carbohydrate oxidation rate but suppressed the fat oxidation rate (Pmeal < 0.05), while its postprandial glucose response was attenuated by bicycling (-0.31 ± 0.03 mmol/L; Pexercise < 0.001). We identified 69 metabolites as key features in discriminating between the 3 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 the hyperglycemia induced by a high-carbohydrate meal. Overweight/obese men were more responsive to the meal challenges than normal-weight men. This trial was registered at clinicaltrials.gov as NCT03231618.

Keywords: amino acids; energy expenditure; fat oxidation; macronutrients; untargeted metabolomics.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity*
  • Adolescent
  • Adult
  • Biomarkers
  • Blood Glucose / metabolism
  • Cross-Over Studies
  • Energy Metabolism
  • Humans
  • Insulin
  • Male
  • Meals
  • Middle Aged
  • Obesity / metabolism
  • Overweight* / metabolism
  • Postprandial Period / physiology
  • Young Adult


  • Biomarkers
  • Blood Glucose
  • Insulin

Associated data

  • ClinicalTrials.gov/NCT03231618