Acute response to a high-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-fat, 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-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 the myeloperoxidase products L-methionine S-oxide, 3-(4-hydroxyphenyl)pyruvate, and L-homocitrulline, in gut microbiota metabolites such as hydroxy-isocaproic acid, and 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-fat high-refined carbohydrate meal, and then a return to baseline reflecting metabolic flexibility.