Synthetic alkaloid treatment influences the intestinal epithelium and mesenteric adipose transcriptome in Holstein steers

Authors: MCLEAN, KYLE - UNIVERSITY OF KENTUCKY; Baldwin, Ransom - Randy; Li, Congjun - Cj; Klotz, James; EDWARDS, J - UNIVERSITY OF TENNESSEE; MCLEOD, KYLE - UNIVERSITY OF KENTUCKY

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/29/2020
Publication Date: 9/11/2020
Citation: McLean, K.J., Baldwin, R.L., Li, C., Klotz, J.L., Edwards, J.L., McLeod, K.R. 2020. Synthetic alkaloid treatment influences the intestinal epithelium and mesenteric adipose transcriptome in Holstein steers. Frontiers in Veterinary Science. 7. Article 615. https://doi.org/10.3389/fvets.2020.00615.
DOI: https://doi.org/10.3389/fvets.2020.00615

Interpretive Summary: Tall fescue infected with endophyte is widely present on the grazing land of the United States but it is known to decrease animal productivity due to high ergot alkaloid ingestion from the endophyte infected plants and represents a significant economical loss the industry. Sixteen Holstein steers were used to determine if a synthetic alkaloid, bromocriptine, would alter the expression of genes in the small intestine and mesenteric adipose. On d 0, steers were assigned to one of two treatments: control (CON; saline only) or bromocriptine (BROMO; 0.1 mg/kg BW bromocriptine mesylate injected intramuscularly every 3 d for 30 d). Steers were treated with either control (CON) or BROMO (bromocriptine)treatement and when euthanized, small intestinal sections of jejunal epithelium and mesenteric fat were collected for RNA isolation. Transcriptome analysis was completed using a procedure called RNA-Sequencing to determine if BROMO tissue gene expression was different from the CON treatment. Only two genes were found to be different within the intestinal epithelium but there were 20 differentially expressed genes in the mesenteric adipose tissue. Using a powerful bioinformatics program call Ingenuity Pathway Analysis, functions related to cell movement, cell development, cell growth and proliferation, cell death, and overall cellular function and maintenance were identified as categories influenced most by BROMO treatment within the intestinal epithelium. The categories within mesenteric adipose most affected were antigen presentation, protein synthesis, cell death, cell movement, and cell to cell signaling and interaction. In conclusion, BROMO treatment influenced the intestinal epithelium and mesenteric adipose transcriptome and we have identified genes and pathways influential to the negative effects associated with alkaloid exposure which are important to beef production.

Technical Abstract: Holstein steers (n = 16) were used to determine if a synthetic alkaloid, bromocriptine, would alter the transcriptome of small intestine and adjacent mesenteric adipose. On d 0, steers were assigned to one of two treatments: control (CON; saline only) or bromocriptine (BROMO; 0.1 mg/kg BW bromocriptine mesylate injected intramuscularly every 3 d for 30 d). Steers were slaughtered and midpoint sections of jejunal epithelium and associated mesenteric fat were collected for RNA isolation. Transcriptome analysis was completed via RNA-Seq to determine if BROMO differed compared with CON within intestinal epithelium or mesenteric adipose mRNA isolates. Differential expression thresholds were set at a significant P - value (P < 0.05) and a fold change >= 1.5. Only two genes were differentially expressed within the intestinal epithelium but there were 20 differentially expressed genes in the mesenteric adipose tissue (6 up regulated and 14 down regulated). Functions related to cell movement, cell development, cell growth and proliferation, cell death, and overall cellular function and maintenance were the top 5 functional molecular categories influenced by BROMO treatment within the intestinal epithelium. The top molecular categories within mesenteric adipose were antigen presentation, protein synthesis, cell death, cell movement, and cell to cell signaling and interaction. In conclusion, BROMO treatment influenced the intestinal epithelium and mesenteric adipose transcriptome and identified genes and pathways influential to the effects associated with alkaloid exposure which are important to beef production.