Plasma metabolomics and proteomics profiling after a postprandial challenge reveal subtle diet effects on human metabolic status Linette PellisMarjan J. van ErkBen van OmmenGertruud C. M. Bakker • Henk F. J. HendriksNicole H. P. CnubbenRobert KleemannEugene P. van Someren • Ivana BobeldijkCarina M. RubinghSuzan Wopereis

Abstract We introduce the metabolomics and proteomicsbased Postprandial Challenge Test (PCT) to quantify thepostprandial response of multiple metabolic processes inhumans in a standardized manner. The PCT comprisedconsumption of a standardized 500 ml dairy shake con-taining respectively 59, 30 and 12 energy percent lipids,carbohydrates and protein. During a 6 h time course afterPCT 145 plasma metabolites, 79 proteins and 7 clinicalchemistry parameters were quantified. Multiple processesrelated to metabolism, oxidation and inflammation reactedto the PCT, as demonstrated by changes of 106 metabo-lites, 31 proteins and 5 clinical chemistry parameters. ThePCT was applied in a dietary intervention study to evaluateif the PCT would reveal additional metabolic changescompared to non-perturbed conditions. The study consistedof a 5-week intervention with a supplement mix of anti-inflammatory compounds in a crossover design with 36overweight subjects. Of the 231 quantified parameters, 31had different responses over time between treated andcontrol groups, revealing differences in amino acidmetabolism, oxidative stress, inflammation and endocrinemetabolism. The results showed that the acute, short termmetabolic responses to the PCT were different in subjectson the supplement mix compared to the controls. The PCTprovided additional metabolic changes related to the die-tary intervention not observed in non-perturbed conditions.Thus, a metabolomics based quantification of a standard-ized perturbation of metabolic homeostasis is more infor-mative on metabolic status and subtle health effectsinduced by (dietary) interventions than quantification of thehomeostatic situation.Keywords Postprandial challenge Metabolic profiling Proteomic profiling Plasma1 IntroductionThe physiological and biochemical response to a dietaryperturbation is complex. It includes energy storage mostlyorchestrated by insulin and involves metabolic switches inseveral organs like liver, muscle and adipose tissue, accom-panied by several compensating processes such as inflam-mation and oxidative stress (Carroll and Schade 2003;Esposito et al. 2003; Nappo et al. 2002;Nerietal.2005;Wybranska et al. 2003). Many of these processes share path-ways and control mechanisms that are common to metabolic,inflammatoryandoxidativestressprocesses.Forinstance,theresponse to a ‘‘simple’’ glucose bolus involves modulation ofglucose itself, triglycerides, blood pressure, cholesterol,inflammation and oxidation (Nakatsuji et al. 2010).The postprandial response depends on, and involvesmultiple factors. Multiple processes related to metabolism,inflammation and oxidation are affected (Lundman et al.2007). The type, nature and amount of fat influences lipid