Acute response to a high-saturated-fat, high-refined-carbohydrate meal in healthy young men shows novel perturbation of multiple metabolic and defense pathways

Abstract

Background: Metabolic flexibility is characterized by a complex response in blood markers rapidly returning to baseline after a high-saturated-fat, high-refined-carbohydrate meal, and this adaptability is progressively lost as chronic metabolic dysfunction develops. Objective: To comprehensively profile the postprandial response and identify novel potential biomarkers related to defense, oxidative stress and other processes, to better define metabolic flexibility. Methods: Conventional methods as well as metabolomics and proteomics were used to profile the response in 12 healthy men to a high-saturated-fat, high-refined-carbohydrate meal, at hourly time points both before and after consumption. Results: In addition to the expected changes in glucose, insulin, triglycerides, fatty acids and myeloperoxidase, we observed multiple previously unreported changes in the plasma proteome, including a compromised “cellular oxidant detoxification” pathway (55 proteins) at 4 and 5 hours after the meal. Between individuals, the magnitude of the decrease in Cu-Zn-superoxide dismutase protein was associated with plasma postprandial glucose area-under-the-curve (r = −0.767, p = 0.004). In contrast, the peripheral blood mononuclear cell proteome showed minimal changes over 6 hours. Through plasma metabolomic analysis, we observed many novel postprandial changes with potential use as biomarkers, most notably increases in oxidative stress-related products such as myeloperoxidase putative products L-methionine S-oxide, 3-(4-hydroxyphenyl)pyruvate, and L-homocitrulline and in gut microbiota metabolites such as hydroxy-isocaproic acid, as well as a sustained elevation of phenylalanine, tyrosine, and branched chain amino acids at 6 hours. Conclusion: These data indicate a complex diminution of plasma defense proteins after a high-saturated fat high-refined carbohydrate meal, and then a return to baseline reflecting metabolic flexibility in the cohort of healthy young men. However, the data also show that some risk markers and stress products are still elevated 6 hours after the meal. The data provide a valuable resource for future postprandial metabolomic studies assessing the protective effect of nutrients and phytochemicals on postprandial stresses, and enabling comparisons between healthy and compromised populations. The clinical trial registry number is ACTRN12619000929101 (www.anzctr.org.au).