The level of dietary energy fed prepartum can alter the physiological adaptations to the transition period both in dairy and beef cattle. Transcriptome profiling studies of peripartal cattle also demonstrated molecular adaptations in this organ some of which could alter its function,Zoxazolamine immune response and lipid metabolism. The limited bioinformatics analyses performed in previous studies indicated that moderate overfeeding of energy pre-partum results in transcriptional changes predisposing cows to fatty liver and potentially compromising liver health early postpartum. The aggregation of the transcriptomics dataset from cows fed recommended or different levels of energy prepartum revealed an extremely large effect of OF or restricting energy prepartum on the transcriptome adaptations during the transition period with a very modest effect observed when cows were fed recommended levels of energy. Due to the more pronounced effect on the liver transcriptome of prepartal OF or RE relative to feeding to requirements, in the present work we took advantage of the advancements in bioinformatics and statistical tools to re-analyze microarray data from the Zebularine liver of OF and RE cows from the previously published study from Loor et al.. The functional analysis of DEG between the two treatments at each time point during the transition period was performed using both the Dynamic Impact Approach, a novel bioinformatics approach developed by Bionaz et al., and the classical enrichment analysis approach by means of Database for Annotation, Visualization and Integrated Discovery coupled with previously published and new blood biomarkers. In addition, we used Ingenuity Pathway Analysis to study the upstream regulators of transcriptomics differences. The primary aim of the present study was to propose an all-encompassing dynamic model to explain the main effects of prepartal dietary management approaches on the physiological adaptations of transition dairy cattle. We reported previously that prepartal high dietary energy vs. feed restriction markedly increased prepartal insulin concentration and early postpartum concentration of NEFA, BHBA, total protein, and liver TAG.