Propylene Glycol Alleviates Oxidative Stress and Enhances Immunity in Ketotic Cows through Modulating Amino Acid and Lipid Metabolism

Abstract

This study investigates the impact of propylene glycol (PRG) on ketotic cows, focusing on alleviating oxidative stress and enhancing immunity through modulating amino acid and lipid metabolism. Ketosis, a prevalent metabolic disease in dairy cows, negatively affects productivity and health. PRG, known for its gluconeogenic properties, was administered to cows with ketosis daily for three days and compared to an untreated group. Serum samples were taken to measure the biochemical parameters, and metabolomic and lipidomic analyses were performed with ultra-high-performance liquid chromatography-mass spectrometry. The results showed significant reductions in serum non-esterified fatty acids, beta-hydroxybutyrate, and C-reactive protein levels, alongside increased glucose, anti-inflammatory factor interleukin-10, superoxide dismutase, and glutathione peroxidase activities. Metabolomic and lipidomic analyses revealed significant alterations, including increased levels of glucogenic amino acids like glutamate and proline, and decreased levels of ceramide species. A pathway analysis indicated that PRG affects multiple metabolic pathways, including alanine, aspartate, glutamate metabolism, and sphingolipid metabolism. These findings suggest that PRG not only mitigates oxidative stress, but also enhances immune function by restoring metabolic homeostasis. This study provides valuable insights into the biochemical mechanisms underlying PRG's therapeutic effects, offering potential strategies for the effective management and treatment of ketosis in dairy cows.

Keywords: dairy cows; ketosis; lipid metabolism; propylene glycol.

Figure 1

Multivariate analysis score plots of serum metabolites. (A) Score plot of the principal component analysis (PCA). (B) Score plot of orthogonal partial least-squares discriminant analysis (OPLS-DA). CON, ketosis cows without treatment; PRG, ketosis cows with propylene glycol drenching.

Figure 2

Serum metabolome analysis. (A) Volcano plot of serum metabolites. (B) The VIP loading plot represents the variable importance in projection (VIP) of each differential metabolite: red represents a high concentration and blue represents a low concentration. (C) Examples of boxplots of differential amino acid metabolites. CON, ketosis cows without treatment; PRG, ketosis cows with propylene glycol drenching; VIP, variable importance in projection. * p < 0.05.

Figure 3

Overview of serum lipidomic analysis. (A) Number of lipid species within each identified lipid class. (B) Principal component analysis (PCA) of mouse serum lipidome. (C) Score plot of orthogonal partial least-squares discriminant analysis (OPLS-DA). CON, ketosis cows without treatment; PRG, ketosis cows with propylene glycol drenching.

Figure 4

Identification of serum differential lipid species. (A) Volcano plot showing differential lipid metabolites. (B) Differential lipid species within each identified lipid class. (C) Differential sphingolipid species. CON, ketosis cows without treatment; PRG, ketosis cows with propylene glycol drenching; VIP, variable importance in projection. * p < 0.05; ** p < 0.01, *** p < 0.001.

Figure 5

Metabolic pathway analysis and association analysis. (A) Pathway analysis result for differential metabolites and lipids between PRG versus CON. (B) Association analysis between differential serum biochemical parameters and differential metabolites related to amino acid and energy metabolism. (C) Association analysis between differential serum biochemical parameters and differential sphingolipid species (top 20 of VIP). * p < 0.05, ** p < 0.01, *** p < 0.001. NEFA, non-esterified fatty acid; BHBA, β-hydroxybutyric acid; RQUICKI, revised quantitative insulin sensitivity check index; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; LPS, lipopolysaccharide; CRP, C-reactive protein; IL, interleukin; VIP, variable importance in projection.