Transcriptome as marker for nutrition-related health: added value of time course analyses during challenge tests before and after energy restriction

Phenotypic flexibility is used as a measure for health and can be studied during nutritional challenge tests. Changes in gene expression are early markers and give insight into mechanisms. Energy restriction (ER) has a variety of beneficial health effects and can be used to investigate different health states to study postprandial changes during challenge tests. Objective: We aimed to determine the postprandial effects of a 20% ER diet on whole genome expression profiles of peripheral blood mononuclear cells (PBMCs). Materials and methods: 72 healthy, overweight men and women, aged 50-65, were subjected to an oral glucose tolerance test (OGTT) and a mixed meal test (MMT), before and after a 12 week intervention with either a 20% ER diet or a control diet. Total RNA from PBMCs was isolated at fasting, and at postprandially during the OGTT at 30, 60, and 120 min and during the MMT at 60, 120, 240, and 360 min. RNA of all time points was used to evaluate whole genome gene expression response using Affymetrix microarrays, resulting in a number of 1231 arrays. Results and conclusions: Upon 20% ER, gene sets involved in OXPHOS, cell adhesion, energy metabolism, immune system, cell cycle, and DNA replication were increased. Upon an OGTT, OXPHOS, cell adhesion, and DNA replication gene sets were decreased after ER. Also, some postprandial effects seem to happen in the control group, but at a later stage. We concluded that ER increased phenotypic flexibility by means on increased use of OXPHOS pathways, and that the response to an OGTT seemed faster upon ER than upon a control diet. Microarray analysis was performed on peripheral blood mononuclear cells (PBMC) isolated from 72 healthy overweight men and women that were subjected to an oral glucose tolerance test and mixed meal test before, and after a 12 week 20% energy restriction or control intervention. A total of 14-18 samples per subject were used for microarray analysis.