Lipopolysaccharide (LPS) is a common pathogenic agent that causes many diseases and metabolic disorders. Hypoglycemia is often observed when animals are infected with LPS. To explore the influence of LPS on blood glucose and hepatic gluconeogenesis in goats, 12 goats were randomly assigned to 1 of 2 groups: the LPS-treated group (60 μg/kg BW of LPS; jugular vein injections) or the control group (saline vehicle; jugular vein injections). Blood samples were collected from jugular veins at 0, 1, 2, 4, 6, and 8 h, and liver tissue samples were biopsied 8 h after the injections. The dynamic changes in blood glucose levels as well as key hepatic gluconeogenic enzyme mRNA and protein expression, ATP and ADP levels, and glutathione reductase (GR) activity were determined. The results showed that blood glucose levels in the LPS group were dramatically reduced after an initial, short-term increase. In liver tissue, the mRNA of key gluconeogenic enzymes, phosphoenolpyruvate carboxykinase 1 (PEPCK1;P < 0.05), fructose-1,6-bisphosphatase 1 (FBP1;P < 0.01), pyruvate carboxylase (PCB;P < 0.05), and acyl-CoA synthetase short-chain family member 3 (ACSS3; < 0.01), in the related pathways and PPAR-γ coactivator 1α (PGC-1α;P < 0.05) were decreased in the LPS group compared with those in the control group, whereas glucose-6-phosphatase (G6Pase-α) was not different (P > 0.05). The protein expression of PEPCK1 decreased (P < 0.01), whereas that of G6Pase-α increased (P < 0.05) significantly. The ratio of ADP to ATP ( < 0.05) and the activity of GR (P < 0.01) were markedly increased in the LPS group compared with those in controls. This research showed that LPS markedly affects and reduces blood glucose in dairy goats. The crucial reasons for the marked change in blood glucose are the altered expression of key gluconeogenic enzymes in different pathways and of essential factors associated with gluconeogenesis in the liver.

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.

No abstract