title: Epigenetic mechanisms contribute to the expression of immune related genes in the livers of dairy cows fed a high concentrate diet.
abstract: OBJECTIVE
  Epigenetic 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.
  
  
  METHODS
  In 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).
  
  
  RESULTS
  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 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.
  
  
  CONCLUSIONS
  After 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.
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Guangjun
authors: G
authors: Chang
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Kai
authors: K
authors: Zhang
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Tianle
authors: T
authors: Xu
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Di
authors: D
authors: Jin
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Junfei
authors: J
authors: Guo
authors: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Su
authors: S
authors: Zhuang
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, P. R. China.
authors: Xiangzhen
authors: X
authors: Shen
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D042002:Chromatin Assembly and Disassembly; D018899:CpG Islands; D019175:DNA Methylation; D004032:Diet; D044127:Epigenesis, Genetic; D015870:Gene Expression; D056426:Genetic Loci; D006863:Hydrogen-Ion Concentration; D007109:Immunity / Q000235:genetics*; D008070:Lipopolysaccharides / Q000737:chemistry; D008099:Liver / Q000276:immunology* / Q000378:metabolism*; D008892:Milk; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012417:Rumen / Q000737:chemistry; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014157:Transcription Factors