Characterisation of fasting and postprandial NMR metabolites: insights from the ZOE PREDICT 1 Study

Bermingham, K. M.; Mazidi, M.; Franks, P. W.; Maher, T.; Valdes, A. M.; Linenberg, I.; Wolf, J.; Hadjigeorgiou, G.; Spector, T. D.; Menni, C.; Ordovas, J. M.; Berry, S. E.; Hall, W. L.

doi:10.1101/2022.11.14.516406

bioRxiv · 10.1101/2022.11.14.516406

Characterisation of fasting and postprandial NMR metabolites: insights from the ZOE PREDICT 1 Study

Bermingham, K. M.·Mazidi, M.·Franks, P. W.·Maher, T.·Valdes, A. M.·Linenberg, I.·Wolf, J.·Hadjigeorgiou, G.·Spector, T. D.·Menni, C.·Ordovas, J. M.·Berry, S. E.·Hall, W. L.

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Abstract

BackgroundPostprandial metabolomic profiles and their inter-individual variability are not well characterised. Here we describe postprandial metabolite changes, their correlations with fasting values and their inter- and intra-individual variability following a standardised meal in the ZOE PREDICT 1 cohort. MethodsIn the ZOE PREDICT 1 study (n = 1,002 (NCT03479866)), 250 metabolites, mainly lipids, were measured by Nightingale NMR panel in fasting and postprandial (4 and 6 h after a 3.7 MJ mixed nutrient meal, with a second 2.2 MJ mixed nutrient meal at 4 h) serum samples. For each metabolite, inter- and intra-individual variability over-time was evaluated using linear mixed modelling and intraclass-correlation coefficients (ICC) calculated. ResultsPostprandially, 85% (of 250 metabolites) significantly changed from fasting at 6h (47% increased, 53% decreased; Kruskal-Wallis), with 37 measures increasing by >25%, and 14 increasing by >50%. The largest changes were observed in very large lipoprotein particles and ketone bodies. Seventy-one percent of circulating metabolites were strongly correlated (Spearmans rho >0.80) between fasting and postprandial timepoints, and 5% were weakly correlated (rho <0.50). The median ICC of the 250 metabolites was 0.91 (range 0.08-0.99). The lowest ICCs (ICC<0.40, 4% of measures) were found for glucose, pyruvate, ketone bodies ({beta}-hydroxybutyrate, acetoacetate, acetate) and lactate. ConclusionsIn this large-scale postprandial metabolomic study, circulating metabolites were highly variable between individuals following a mixed challenge meal. Findings suggest that a meal challenge may yield postprandial responses divergent from fasting measures, specifically for glycolysis, essential amino acid, ketone body and lipoprotein size metabolites.

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Bermingham, K. M., Mazidi, M., Franks, P. W., Maher, T., Valdes, A. M., Linenberg, I., Wolf, J., Hadjigeorgiou, G., Spector, T. D., Menni, C., Ordovas, J. M., Berry, S. E., Hall, W. L.. 2022-11-15. Characterisation of fasting and postprandial NMR metabolites: insights from the ZOE PREDICT 1 Study. https://doi.org/10.1101/2022.11.14.516406

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