Integrative hepatic metabolomics and proteomics reveal insights into the mechanism of different feed efficiency with high or low dietary forage levels in Holstein heifers.

Feed efficiency (FE) can be affected by dietary composition, management, and metabolic conditions. The liver is the central metabolic organ in cattle; however, specific metabolic changes in the liver under different dietary forage levels have not been clarified. Therefore, this study aimed to investigate the hepatic physiology mechanisms of high or low dietary forage levels (80% or 20% forage, namely S80 and S20) on FE in dairy heifers using integrative metabolomic and proteomic methods. Feed efficiency was lower in the S80 group than the S20 group. A total of 29 metabolites and 60 proteins were significantly different between the liver samples of the two groups. Fourteen selected proteins were analyzed using parallel reaction monitoring to confirm the reliability of proteomic analysis. Integrative functional analysis of differentially expressed metabolites/proteins confirmed the enhanced hepatic ability of fatty acid oxidation, amino acid metabolism, pentose phosphate pathway, gluconeogenesis, ketone bodies synthesis, and oxidative stress defense in the S80 heifers. These metabolic pathways are associated with FE in ruminants. Thus, our results suggested that the aforementioned metabolic pathways may be responsible for the reduced FE in heifers fed high levels of forage. BIOLOGICAL SIGNIFICANCE: Improving the efficiency of animal production is a continuously urgent mission of all agricultural producers. Limit-feeding high concentrate diets to heifers is considered as an effective way to improve feed efficiency in heifers' raising, which can not only decrease the feeding and management cost but also relieve some environmental problems. However, the detailed metabolic and physiological changes and mechanisms associated with this strategy remain to be further characterized even some transcriptomics and microbiology work have been done. For extending the knowledge towards this strategy, an integrative metabolomic and proteomic method was used to investigate the hepatic physiology mechanisms of high or low dietary forage levels on feed efficiency in dairy heifers. Enhanced hepatic ability of fatty acid oxidation, amino acid metabolism, pentose phosphate pathway, gluconeogenesis, ketone bodies synthesis, and oxidative stress defense were found in high forage consumed heifers, which were all related to energy utilization in ruminants and might be responsible for the reduced feed efficiency. Understanding the molecular mechanisms regulating the hepatic metabolism in high or low forage fed heifers may help to design alternative feeding or management strategies that improve feed efficiency.