Abstract
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.
Highlights
In the dairy industry, it is currently a common practice to feed a high concentrate (HC) diet to lactating cows to meet their energy requirements to support high milk production
After 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 low concentrate (LC) group
After HC diet feeding, LPS derived from the digestive tract translocated to the liver via the portal vein, enhancing hepatic immune gene expression
Summary
It is currently a common practice to feed a high concentrate (HC) diet to lactating cows to meet their energy requirements to support high milk production. This practice might increase short-term economic efficiency, it is not a beneficial practice for the health of cows. The consumption of a HC diet causes a series of changes that involve a significant depression of pH and increased lipopolysacchrides (LPS) in the rumen and intestine, as well as the elevation of acute phase proteins (APPs), including LPS-binding protein (LBP), serum anyloid A (SAA), and haptoglobin (Hp), in the peripheral blood [6]. Many hazardous substances are released in the digestive tract and translocate into the bloodstream during feeding with a HC diet, LPS is thought to be the major contributor to systemic inflammation because most LPS is released by Gram-negative bacteria, which are the main bacterial community in the digestive tract of cows [10]
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