Synthetic Alkaloid Treatment Influences the Intestinal Epithelium and Mesenteric Adipose Transcriptome in Holstein Steers

Abstract

Holstein steers (n = 16) were used to determine if a synthetic alkaloid, bromocriptine, would alter the transcriptome of the 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 (six 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 five 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.

Effects of Bromocriptine on Glucose and Insulin Dynamics in Normal and Insulin Dysregulated Horses

“…Bromocriptine administration reduced circulating prolactin concentrations in all horses, indicative that our treatment protocol was successful. Sharing a high degree of structural homology with dopamine, the inhibitory effect of bromocriptine on pituitary prolactin secretion has been documented extensively in many species, including horses ( 18 , 19 , 33 , 34 ). In accordance with recent data in cattle ( 17 ), prolactin levels in all horses sharply declined during the first week of bromocriptine treatment and remained at nadir throughout the entire study period.…”

“…The bromocriptine treatments were given as intramuscular injections on alternate sides the neck every 3 days for 14 days (five injections total) at a rate of 0.1 mg/kg BW. This dosing regimen has been shown to maintain sustained reduction in prolactin in cattle ( 16 – 18 ). Similar doses have also been used in horses to study the effects of bromocriptine on plasma prolactin and progesterone ( 19 ) and thyroid hormone concentrations ( 20 ).…”

Endophyte Infected Tall Fescue: Plant Symbiosis to Animal Toxicosis

“…It has been proposed that ergot alkaloids can alter lipid metabolism, adipose composition, and increase the occurrence of necrotic fat deposits (124), but necrotic fat has only been reported in abdominal fat deposits (125). RNA sequencing analysis from steers treated with the synthetic alkaloid bromocriptine has revealed 20 differentially expressed genes (DEG) within the mesenteric adipose and two within the intestinal epithelium (118). Changes within the intestinal epithelium included upregulation of genes indicated in increased lymphocyte trafficking and homing, which may suggest increased immune activity, and downregulation of genes indicated in transport and metabolism of long chain fatty acids and overall lipid metabolism (118).…”

“…RNA sequencing analysis from steers treated with the synthetic alkaloid bromocriptine has revealed 20 differentially expressed genes (DEG) within the mesenteric adipose and two within the intestinal epithelium (118). Changes within the intestinal epithelium included upregulation of genes indicated in increased lymphocyte trafficking and homing, which may suggest increased immune activity, and downregulation of genes indicated in transport and metabolism of long chain fatty acids and overall lipid metabolism (118). Of the DEGs found in the mesenteric adipose, 14 were downregulated genes whose functions include enzymes, transporters, ion channels, cytokines, and other immune response molecules; and six were up regulated genes with identified functions of enzyme activity, molecular transport, transmembrane receptors, cytokines, and other unknown functions (118).…”

“…Changes within the intestinal epithelium included upregulation of genes indicated in increased lymphocyte trafficking and homing, which may suggest increased immune activity, and downregulation of genes indicated in transport and metabolism of long chain fatty acids and overall lipid metabolism (118). Of the DEGs found in the mesenteric adipose, 14 were downregulated genes whose functions include enzymes, transporters, ion channels, cytokines, and other immune response molecules; and six were up regulated genes with identified functions of enzyme activity, molecular transport, transmembrane receptors, cytokines, and other unknown functions (118). None of the DEGs identified had a direct effect on vascularity, but the direct involvement of some genes in immune response suggests that abdominal effects, such as necrotic fat, could be a result of persistent activation of the immune system.…”