Dataset Information

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.

SUBMITTER: McLean KJ

PROVIDER: S-EPMC7518393 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

McLean Kyle J KJ Baldwin Ransom L RL Li Cong-Jun CJ Klotz James L JL Edwards J Lannett JL McLeod Kyle R KR

Frontiers in veterinary science 20200911

Holstein steers (<i>n</i> = 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 ...[more]

PMID: 33062652

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Project description:Background:Dairy cows can readily overconsume dietary energy during most of the prepartum period, often leading to higher prepartal concentrations of insulin and glucose and excessive body fat deposition. The end result of these physiologic changes is greater adipose tissue lipolysis post-partum coupled with excessive hepatic lipid accumulation and compromised health. Although transcriptional regulation of the adipose response to energy availability is well established in non-ruminants, such regulation in cow adipose tissue depots remains poorly characterized. Results:Effects of ad-libitum access to high [HIGH; 1.62 Mcal/kg of dry matter (DM)] or adequate (CON; 1.35 Mcal/kg of DM) dietary energy for 8 wk on mesenteric (MAT) and subcutaneous (SAT) adipose tissue transcript profiles were assessed in non-pregnant non-lactating Holstein dairy cows using a 13,000-sequence annotated bovine oligonucleotide microarray. Statistical analysis revealed 409 and 310 differentially expressed genes (DEG) due to tissue and diet. Bioinformatics analysis was conducted using the Dynamic Impact Approach (DIA) with the KEGG pathway database. Compared with SAT, MAT had more active biological processes related to adipose tissue accumulation (adiponectin secretion) and signs of pro-inflammatory processes due to adipose tissue expansion and macrophage infiltration (generation of ceramides). Feeding the HIGH diet led to changes in mRNA expression of genes associated with cell hypertrophy (regucalcin), activation of adipogenesis (phospholipid phosphatase 1), insulin signaling activation (neuraminidase 1) and angiogenesis (semaphorin 4G, plexin B1). Further, inflammation due to HIGH was underscored by mRNA expression changes associated with oxidative stress response (coenzyme Q3, methyltransferase), ceramide synthesis (N-acylsphingosine amidohydrolase 1), and insulin signaling (interferon regulatory factor 1, phosphoinositide-3-kinase regulatory subunit 1, retinoic acid receptor alpha). Activation of ribosome in cows fed HIGH indicated the existence of greater adipocyte growth rate (M-phase phosphoprotein 10, NMD3 ribosome export adaptor). Conclusions:The data indicate that long-term ad-libitum access to a higher-energy diet led to transcriptional changes in adipose tissue that stimulated hypertrophy and the activity of pathways associated with a slight but chronic inflammatory response. Further studies would be helpful in determining the extent to which mRNA results also occur at the protein level.

Project description:Performance of dairy cows can be influenced by early life nutrient supply. Adipose tissue is diet sensitive and an important component in that process as it is involved in the regulation of energetic, reproductive and immunological functions. However, it is not clear how early life nutrition alters the molecular regulation of adipose tissue in calves and potentially adult individuals. This study aimed at determining how differences in pre-weaning nutrient supply alter gene expression profiles and physiology in omental adipose tissue. A total of 12 female Holstein calves were fed two levels of milk replacer supply: a restricted amount of 11.72 MJ of metabolizable energy (ME) intake per day (n = 6) or an enhanced amount of 1.26 MJ ME intake per kg of metabolic body weight (BW0.75), resulting in supply from 17.58 to 35.17 MJ ME intake per day (n = 6). All calves had ad libitum access to a commercial calf starter and water. Analysis of the transcriptome profiles at 54 ± 2 days of age revealed that a total of 396 out of 19,968 genes were differentially expressed (DE) between groups (p < 0.001, FDR < 0.1). The directional expression of DE genes through Ingenuity Pathway Analysis showed that an enhanced nutrient supply alters adipose tissue physiology of pre-weaned calves. Several biological functions were increased (Z-score > +2), including Lipid Metabolism (Fatty Acid Metabolism), Cell Cycle (Entry into Interphase, Interphase, Mitosis and Cell Cycle Progression), Cellular Assembly and Organization (Cytoskeleton Formation and Cytoplasm Development) and Molecular Transport (Transport of Carboxylic Acid). These changes were potentially orchestrated by the activation/inhibition of 17 upstream regulators genes. Our findings indicate that adipose tissue of calves under an enhanced nutrient supply is physiologically distinct from restricted calves due to an increased development/expansion rate and also a higher metabolic activity through increased fatty acid metabolism.

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Dataset Information

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

Publications

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

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