The large variability in metabolic responses of dairy cows with similar genetic background and breeding system during the transition period (late gestation - early lactation) reflects individual differences in adaptive capacity. Inadequate adaptation of the cow has negative effects on its health as well as on its production and reproductive performances. This generates economic/profitability losses for the dairy industry as well as animal welfare concerns. Despite numerous studies, deciphering molecular mechanism that promote coordinated and adapted metabolic responses or disorders during the transition period of dairy cows is still a challenge that needs to be tackled. The originality of the FAIR_Cow project, is to consider plasma free fatty acids not only as indicators of metabolic status (and risk of disorders) but also as biologically active molecules acting as coordinators of metabolic responses. Furthermore, it is also hypothesized that free fatty acid receptors (FFARs), newcomers to free fatty acid signaling, allow free fatty acids to mediate their diversity of actions at the cellular level. Thus, through the FAIR_Cow project, key free fatty acids related to the adaptive capacities of dairy cows will be identified. The cellular mechanisms regulated by these key free fatty acids will be elucidated. The relative contribution of FFARs to the mechanism of action of free fatty acids at the cellular level will be quantified and associated biomarkers of FFAR-dependent signaling pathways will be identified. Finally, aptamer-based detection methods will be developed in order to allow to identify physiological processes regulated by FFARs in vivo. Knowledge acquired during the FAIR_Cow project will pave the way for a better understanding of the large variability of metabolic responses of dairy cows during the challenging transition period. Finally, the tools for phenotyping the adaptive capacities of dairy cows developed during the FAIR_Cow project will open up new perspectives for dairy herd management at the individual level.