Metabolomics Reveals that the Type of Protein in a High-Fat Meal Modulates Postprandial Mitochondrial Overload and Incomplete Substrate Oxidation in Healthy Overweight Men

J Nutr. 2018 Jun 1;148(6):876-884. doi: 10.1093/jn/nxy049.

Abstract

Background: A meal rich in saturated fatty acids induces a postprandial metabolic challenge. The type of dietary protein may modulate postprandial metabolism.

Objective: We studied the effect of dietary protein type on postprandial changes in the metabolome after a high-fat meal.

Methods: In a 3-period, crossover, postprandial study, 10 healthy overweight men with an elevated waist circumference (>94 cm) ingested high-fat meals made up of cream fat (70% of energy), sucrose (15% energy), and protein (15% energy) from either casein (CAS), whey protein (WHE), or α-lactalbumin-enriched whey protein (LAC). Urine collected immediately before and 2, 4, and 6 h after the meal was analyzed for metabolomics, a secondary outcome of the clinical study. We used mixed-effect models, partial least-square regression, and pathway enrichment analysis.

Results: At 4 and 6 h after the meal, the postprandial metabolome was found to be fully discriminated according to protein type. We identified 17 metabolites that significantly explained the effect of protein type on postprandial metabolomic changes (protein-time interaction). Among this signature, acylcarnitines and other acylated metabolites related to fatty acid or amino acid oxidation were the main discriminant features. The difference in metabolic profiles was mainly explained by urinary acylcarnitines and some other acylated products (protein type, Ps < 0.0001), with a dramatically greater increase (100- to 1000-fold) after WHE, and to a lesser extent after LAC, as compared with CAS. Pathway enrichment analysis confirmed that the type of protein had modified fatty acid oxidation (P < 0.05).

Conclusion: Taken together, our results indicate that, in healthy overweight men, the type of protein in a high-fat meal interplays with fatty acid oxidation with a differential accumulation of incomplete oxidation products. A high-fat meal containing WHE, but not CAS, resulted in this outpacing of the tricarboxylic acid cycle. This study was registered at clinicaltrials.gov as NCT00931151.

Publication types

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

MeSH terms

  • Adult
  • Cross-Over Studies
  • Fats / administration & dosage*
  • Humans
  • Male
  • Meals*
  • Metabolomics*
  • Middle Aged
  • Postprandial Period
  • Proteins / administration & dosage*
  • Young Adult

Substances

  • Fats
  • Proteins

Associated data

  • ClinicalTrials.gov/NCT00931151