The effects of acute lipopolysaccharide challenge on dairy goat liver metabolism assessed with ¹HNMR metabonomics

Abstract

We investigated the mechanisms mediating hepatic metabolic responses to an acute lipopolysaccharide (LPS) challenge in goats. Guanzhong dairy goats (15) were randomly divided into three groups: control (CTL, saline, 0.2 ml/kg BW), lower dose LPS (LPS-L, 20 μg/kg BW) and higher dose LPS (LPS-H, 40 μg/kg BW). All injections were administered intraperitoneally twice with a 24-h interval. Forty-eight hours after the first injection, blood samples were collected to extract plasma for biochemical analysis, and liver tissues were biopsied and stored in liquid nitrogen for metabonomics analysis. We found that plasma levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin increased (p < 0.05) in both LPS-treated groups, whereas plasma triglyceride, cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein, total protein and albumin levels markedly decreased (p < 0.05). The increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), levels of tumour necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and IL-8 indicated hepatic injury and metabolic dysfunction in some degree. Using proton nuclear magnetic resonance ( H-NMR) metabonomics and the Chenomx NMR suite database, 69 metabolites were detected and identified. Metabolic differences among the groups were determined with pattern recognition analyses using principal component analysis and supervised projection to latent structures discriminant analysis. Pattern recognition analysis distinguished and clustered the metabolite variables from the three groups, finding nine of 69 metabolites that differed significantly between two of the three groups: six from the LPS-L or LPS-H groups differed from CTL and three differed between LPS-L and LPS-H groups. These altered metabolites were closely connected with glucose, lipid and amino acid metabolic pathways in hepatocytes. Based on an analysis of these metabolites and their relevant pathways, the mechanisms and degree of hepatic injury were deduced. Therefore, the metabolic profile was used effectively to detect characteristic hepatic metabolites, discriminate metabolic changes induced by LPS, clarify the mechanisms for the resulting metabolic dysfunctions and provide efficient information to diagnose liver injury.

The hepatic and skeletal muscle ovine metabolomes as affected by weight loss: a study in three sheep breeds using NMR-metabolomics

“…The study, demonstrated the potential of this approach to help create a more systematic metabolome analysis16. Other recent studies in farm animals confirm the potential of NMR technique to metabolomics approaches17181920.…”

Invited review: The influence of immune activation on transition cow health and performance—A critical evaluation of traditional dogmas

“…As mentioned previously, increased circulating TG likely represents a strategy to promote LPS detoxification, as lipoproteins can help efficiently detoxify LPS. In ruminants, LPS-induced changes in TG concentrations are poorly described, as both increased (Ballou et al, 2008;Graugnard et al, 2013) and decreased (Wang et al, 2017) levels have been reported. Discrepancies in the response may be explained by sampling time, as the increase in TG appears to be short lived (Ballou et al, 2008;Graugnard et al, 2013).…”

Serum metabolomics reveal pathways associated with protective effect of ginsenoside Rg3 on immune stress

“…To the best of our knowledge, this is the first study to identify serum metabolites associated with the pathogenesis and the protection against stress in broilers. Previous studies demonstrated LPS challenge caused alterations in lipid and protein metabolism in different animals ( Wan et al, 2017 ; Wang et al, 2017 ; Chirivi et al, 2022 ). In present study, taurolithocholic acid, myristoleic acid, stearoylcarnitine, PC (16:0/16:0), 1-Hexadecyl-sn-glycero-3-phosphocholine and Ser-Arg were significantly altered, suggesting that the abnormal degradation of lipid and protein were involved in the pathogenesis of stress in chicks ( Ozawa et al, 2020 ; Heidenreich et al, 2021 ).…”