With the exception of ‘Notch signaling’ and ‘Hedgehog signaling’ all the pathways involved in signaling communication were more induced in OF vs. RE. The inhibition of ‘Notch signaling’ in OF vs. RE is likely a consequence of the greater lipid accumulation. It has been clearly demonstrated that steatosis in mice inhibits Notch signaling. It is noteworthy that the pathway was already more inhibited in OF vs. RE at 214 d, well-before the greater TAG Cortisone acetate concentration was observed. This indicate that the larger inhibition of the Notch signaling pathway in OF vs. RE prior to the peak of NEFA might have allowed for a greater lipid accumulation postpartum. This idea is supported by the higher induction of ‘MAPK signaling’ in OF vs. RE particularly during early lactation. This pathway is mainly involved in the control of cellular growth and proliferation but it also is essential for the induction of liver steatosis in mouse by cross-talk with the peroxisome proliferator-activated receptor gamma. Although our data seem to support such a role, the expression of PPARc in bovine liver is nearly non detectable relative to the alpha and delta isotypes. The PPAR, particularly PPARa, is considered important in the whole economy of lipid metabolism in liver of mammals,Atropine sulfate including dairy cows during the transition period. Our analysis indicated that the ‘PPAR signaling’ pathway played a role in regulating aspects of lipid metabolism in response to different levels of dietary energy fed prepartum. As commonly observed in monogastrics, the ‘PPAR signaling’ pathway was more induced in liver of RE compared with OF cows. It is noteworthy that the larger activation of ‘PPAR signaling’ in RE vs. OF also was observed at + 14 d, namely due to the higher expression of genes encoding for proteins involved in FA oxidation. These data support a role of PPAR in controlling lipid catabolism in response to prepartal dietary energy level. However, the higher activation of this pathway in RE vs. OF in spite of a lower concentration of plasma NEFA, which should increase its activation, also supports the idea of a liver in RE vs. OF that was better ‘‘primed’’ to respond to the increased NEFA flux postpartum potentially by having a higher metabolic capacity. The use of additional blood biomarkers and novel bioinformatics tools for the analysis of published transcriptomics data provided a more holistic understanding of the role of plane of nutrition during late-pregnancy on hepatic adaptations around the period of parturition.