Abstract
Background The hypothalamus plays a crucial role in the health and productivity of dairy cows,yet studies on its functionality and its impact on peripheral circulation in these animals are relatively scarce,particularly regard-ing dietary interventions.Therefore,our study undertook a comprehensive analysis,incorporating both metabolomics and transcriptomics,to explore the effects of a grain-based diet on the functionality of the hypothalamus,as well as on blood and milk in dairy cows.Results The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E2(PGE2)level as a prominent response to the grain-based diet introduction.Furthermore,the hypothalamic transcriptome profiling showed a notable upregulation in amino acid metabolism due to the grain-based diet.Conversely,the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE2,including phospho-lipase A2(PLA2G4E,PLA2G2A,and PLA2G12B),cyclooxygenase-2(COX2),and prostaglandin E synthase(PTGES).Addi-tionally,the plasma metabolome analysis indicated a substantial decrease in the level of PGE2,along with a decline in adrenal steroid hormones(tetrahydrocortisol and pregnenolone)following the grain-based diet introduction.Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE2 level.Importantly,PGE2 was identified as a critical metabolic marker in the hypothalamus,blood,and milk in response to grain intervention.Correlation analysis demonstrated a significant correlation among meta-bolic alterations in the hypothalamus,blood,and milk following the grain-based diet.Conclusions Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet.