213 Lipopolysaccharide-induced alterations in the liver metabolome of St. Croix and Suffolk sheep

Abstract The development of resistance in parasites due to overuse of anthelmintics has resulted in a marked decrease in the efficacy of these drug classes. Recent research efforts have focused on exploring alternatives such as selection for parasite-resistant breeds with the implication that immunocompetence may align with parasite resistance. Two breeds that are often investigated are the St. Croix (STC), a resistant hair breed, and Suffolk (SUF), a susceptible wool breed sheep. The liver has a vital role in metabolism in the body and metabolizes lipopolysaccharide (LPS), which triggers whole body response through the production of appropriate metabolites, cytokines and immune cells. The objective of this study was to investigate the breed differences in liver metabolome of sheep, with divergent resistance to parasites, in response to LPS. Both STC and SUF sheep (n = 9/breed) were challenged with LPS, intravenously and liver biopsies were collected prior to challenge (HR0), 2 h post-challenge (HR2) and 6 h post-challenge (HR6). Liver tissue samples were subjected to quantitative untargeted metabolome analysis using chemical isotope labelling/ liquid chromatography- mass spectrometry. A total of 874 metabolites were detected and identified. Metabolomics also revealed that 8 pathways (pyrimidine metabolism, pantothenate and CoA biosynthesis, beta-Alanine metabolism, valine, leucine and isoleucine degradation, valine, leucine and isoleucine biosynthesis, folate biosynthesis, arginine and proline metabolism and glutathione metabolism) were altered (P ≤ 0.05) between STC and SUF sheep prior to LPS challenge. A total of 10 pathways (folate biosynthesis, glycine, serine and threonine metabolism, tyrosine metabolism, glycerophospholipid metabolism, purine metabolism, cysteine and methionine metabolism, taurine and hypotaurine metabolism, glutathione metabolism, thiamine metabolism and pantothenate and CoA biosynthesis) were altered (P ≤ 0.05) between STC and SUF sheep at HR 2. Only 2 pathways (glycerophospholipid metabolism and purine metabolism) were altered (P ≤ 0.05) between STC and SUF sheep at HR 6. Results highlight the metabolic differences that exist between breeds as well as indicate the significance of amino acid metabolisms that drive cell proliferation, oxidative stress amelioration and inflammation in response to LPS.