Complementary Muscle Metabolomics and Proteomics of Muscle in Cows With Post‐Calving Ketosis

ABSTRACT Background The muscle tissue of dairy cows is a site of β‐hydroxybutyrate (BHBA) metabolism. The mechanisms underlying the changes in proteins and metabolites in the muscle tissue of cows with ketosis remain unclear. Objectives To elucidate the metabolic and physiological molecular adaptation mechanisms in the muscle tissue of cows with ketosis through metabolomics and proteomics. Animals Six cows diagnosed with ketosis (CK, BHBA ≥ 2.4 mM) and six apparently healthy cows with BHBA < 1 mM (Con), all 1 week postpartum. Methods Prospective cohort observational study. The content of BHBA in whole blood was detected by WST‐1 and TNN methods. HE staining was used to observe the physiological changes in the muscle tissue of cows with ketosis. Metabolomic analysis, proteomic analysis, and WB experiments were employed to identify differential metabolites and proteins. Results The 685 metabolites and 356 proteins were identified to be differentially expressed in the CK group. In the muscle tissue of cows with ketosis, significant changes were observed in processes such as oxidative phosphorylation, PPAR signaling pathway, TCA cycle, amino acid degradation, and fatty acid oxidation. At the protein level, SDHA, SDHB, QCR6, QCR7, and IDH2 were significantly downregulated, while metabolites such as pyruvate were downregulated and BHBA was upregulated. Conclusions and Clinical Importance The TCA cycle and mitochondrial respiratory chain in the muscle tissue of cows with ketosis might be impaired. These results provide valuable insights into the metabolic mechanisms of muscle tissue in cows with ketosis.