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Rumen-derived lipopolysaccharide provoked inflammatory injury in the liver of dairy cows fed a high-concentrate diet.

ABSTRACT: Rumen-derived lipopolysaccharide (LPS) is translocated from the rumen into the bloodstream when subacute ruminal acidosis (SARA) occurs following long-term feeding with a high-concentrate (HC) diet in dairy cows. The objective of this study was to investigate the mechanism of inflammatory responses in the liver caused by HC diet feeding. We found that SARA was induced in dairy cows when rumen pH below 5.6 lasted for at least 3 h/d with HC diet feeding. Also, the LPS levels in the portal and hepatic veins were increased significantly and hepatocytes were impaired as well as the liver function was inhibited during SARA condition. Meanwhile, the mRNA expression of immune genes including TNF receptor associated factor 6 (TRAF6), nuclear factor-kappa B (NF-κB), p38 mitogen-activated protein kinase (MAPK), extracellular regulated protein kinases (ERK) MAPK, Interleukin-1 (IL-1) and serum amyloid A (SAA) in the liver were significantly increased in SARA cows. Moreover, the phosphorylation level of NF-κB p65 and p38 MAPK proteins in the liver and the concentration of Tumor Necrosis Factor (TNF-α), Interleukin-1β (IL-1β) and Interleukin-6 (IL-6) in peripheral blood were obviously increased under SARA condition. In conclusion, the inflammatory injury in the liver caused by LPS that traveled from the digestive tract to the liver through the portal vein after feeding with a HC diet.

SUBMITTER: Guo J

PROVIDER: S-EPMC5564522 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Project description:Periparturient diseases of dairy cows are caused by disproportionate energy metabolism, mineral imbalance, and perturbed immune function. The aim of the present study was to characterize metabolism, innate immune endometrial gene expression, and uterine microbial populations of transition animals receiving normal or restricted energy diets. Pregnant multiparous Holstein cows (n = 14) were randomly assigned to one of the two dietary treatments from 20 d prepartum until 35 d postpartum (DPP). One group was fed a diet providing 100% energy requirements (NE), whereas the other received an energy-restricted diet providing 80% energy requirements (RE). Feed intake, milk yield, body weight, body condition score, temperature, respiratory, and pulse rate were recorded. After calving, blood was collected weekly to analyze nonesterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), and total cholesterol (TC). Endometrial cytobrushes were collected for gene expression analysis of inflammatory markers, microbial populations determination, and cytological evaluation. The restricted energy diet did not alter feed intake or milk yield but changed energy balance and metabolites levels (P < 0.05). In fact, RE animals had high NEFA and BHB levels, and low TC concentrations (P < 0.05). Moreover, RE animals had upregulated gene expression of serum amyloid A3 (SAA3) at 35 DPP (P < 0.05) and CXC chemokine receptor 2 (CXCR2) at 14 DPP (P < 0.01). Interleukin (IL) 1 and IL8 genes were downregulated 14 DPP but upregulated 35 DPP in RE animals, whereas IL6 and lipopolysaccharide-binding protein (LBP) genes were upregulated at 14 DPP (P ≤ 0.05). The most abundant phyla in RE animals (n = 3) were Bacteroidetes and Fusobacteria, whereas Proteobacteria was the least abundant at both 14 and 35 DPP. In conclusion, it can be speculated that energy balance is one of the main drivers for uterine inflammation by affecting metabolism, immune function, and uterine microbiota. However, these findings should be validated in a larger sample size.

Project description:PurposeEpigenetic modifications critically regulate the expression of immune-related genes in response to inflammatory stimuli. It has been extensively reported that a high concentrate (HC) diet can trigger systemic inflammation in dairy cows, yet it is unclear whether epigenetic regulation is involved in the expression of immune genes in the livers of dairy cows. This study aimed to investigate the impact of epigenetic modifications on the expression of immune-related genes.Experimental designIn eight mid-lactating cows, we installed a rumen cannula and catheters of the portal and hepatic veins. Cows were randomly assigned to either the treatment group fed a high concentrate (HC) diet (60% concentrate + 40% forage, n = 4) or a control group fed a low concentrate (LC) diet (40% concentrate + 60% forage, n = 4).ResultsAfter 10 weeks of feeding, the rumen pH was reduced, and levels of lipopolysaccharide (LPS) in the rumen, and portal and hepatic veins were notably increased in the HC group compared with the LC group. The expression levels of detected immune response-related genes, including Toll-like receptor 4 (TLR4), cytokines, chemokines, and acute phase proteins, were significantly up-regulated in the livers of cows fed a HC diet. Chromatin loosening at the promoter region of four candidate immune-related genes (TLR4, LPS-binding protein, haptoglobin, and serum amyloid A3) was elicited, and was strongly correlated with enhanced expression of these genes in the HC group. Demethylation at the promoter region of all four candidate immune-related genes was accompanied by chromatin decompaction.ConclusionAfter HC diet feeding, LPS derived from the digestive tract translocated to the liver via the portal vein, enhancing hepatic immune gene expression. The up-regulation of these immune genes was mediated by epigenetic mechanisms, which involve chromatin remodeling and DNA methylation. Our findings suggest that modulating epigenetic mechanisms could provide novel ways to treat systemic inflammatory responses elicited by the feeding of a HC diet.

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Rumen-derived lipopolysaccharide provoked inflammatory injury in the liver of dairy cows fed a high-concentrate diet.

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