Abstract
Introduction
The effects of lipopolysaccharides (i.e., endotoxin; LPS) on metabolism are poorly defined in lactating dairy cattle experiencing hyperlipidemia.
Objectives
Our objective was to explore the effects of acute intravenous LPS administration on metabolism in late-lactation Holstein cows experiencing hyperlipidemia induced by intravenous triglyceride infusion and feed restriction.
Methods
Ten non-pregnant lactating Holstein cows (273 ± 35 d in milk) were administered a single bolus of saline (3 mL of saline; n \(=\) 5) or LPS (0.375 \(\mu\)g of LPS/kg of body weight; n \(=\) 5). Simultaneously, cows were intravenously infused a triglyceride emulsion and feed restricted for 16 h to induce hyperlipidemia in an attempt to model the periparturient period. Blood was sampled at routine intervals. Changes in circulating total fatty acid concentrations and inflammatory parameters were measured. Plasma samples were analyzed using untargeted lipidomics and metabolomics.
Results
Endotoxin increased circulating serum amyloid A, LPS-binding protein, and cortisol concentrations. Endotoxin administration decreased plasma lysophosphatidylcholine (LPC) concentrations and increased select plasma ceramide concentrations. These outcomes suggest modulation of the immune response and insulin action. Lipopolysaccharide decreased the ratio of phosphatidylcholine to phosphatidylethanomanine, which potentially indicate a decrease in the hepatic activation of phosphatidylethanolamine N-methyltransferase and triglyceride export. Endotoxin administration also increased plasma concentrations of pyruvic and lactic acids, and decreased plasma citric acid concentrations, which implicate the upregulation of glycolysis and downregulation of the citric acid cycle (i.e., the Warburg effect), potentially in leukocytes.
Conclusion
Acute intravenous LPS administration decreased circulating LPC concentrations, modified ceramide and glycerophospholipid concentrations, and influenced intermediary metabolism in dairy cows experiencing hyperlipidemia.
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Data Availability
The plasma metabolome and lipidome datasets generated are available on demand in the Cornell Biotechnology Server.
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This work is supported by Agriculture and Food Research Initiative Grant No. 2018-67015-27548 from the USDA National Institute of Food and Agriculture.
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The authors’ responsibilities were as follows: EAH and LHB developed the experimental design and conducted sampling; MED Rubio performed the mass spectrometry analyses; FW analyzed data. FW, AJ, LW and JWM wrote the manuscript. JWM and LHB conceptualized the idea and were responsible for final content. AJ and FW have equal contributions. All authors read and approved the final manuscript.
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Javaid, A., Wang, F., Horst, E.A. et al. Effects of acute intravenous lipopolysaccharide administration on the plasma lipidome and metabolome in lactating Holstein cows experiencing hyperlipidemia. Metabolomics 18, 75 (2022). https://doi.org/10.1007/s11306-022-01928-1
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DOI: https://doi.org/10.1007/s11306-022-01928-1