Influence of postruminal casein infusion and exogenous glucagon-like peptide 2 administration on the jejunal mucosal transcriptome in cattle
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ABSTRACT:
PROVIDER: PRJNA1041853 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26865903_1.fastq.gz | Fastqsanger.gz | |||
| SRR26865903_2.fastq.gz | Fastqsanger.gz | |||
| SRR26865904_1.fastq.gz | Fastqsanger.gz | |||
| SRR26865904_2.fastq.gz | Fastqsanger.gz | |||
| SRR26865905_1.fastq.gz | Fastqsanger.gz |
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Project description:The objective of the current study was to evaluate the effects of postruminal casein infusion and exogenous glucagon-like peptide 2 (GLP-2) administration on transcriptomic pathways and functions of the jejunal mucosa in cattle using next-generation RNA sequencing. Twenty-four Holstein steers [250 ± 23 kg body weight (BW)] received a continuous abomasal infusion of 3.94 g raw corn starch/kg of BW combined with either 0 or 1.30 g casein/kg of BW for 7 d. Steers received subcutaneous injections in two equal portions daily of excipient (0.5% bovine serum albumin) or 100 µg GLP-2/kg of BW per day. At the end of the 7-d treatment period, steers were slaughtered for collection of the jejunal mucosa. Total RNA was extracted from jejunal mucosal tissue, strand-specific cDNA libraries were prepared, and RNA sequencing was conducted to generate 150-bp paired-end reads at a depth of 20 M reads in each direction. Differentially expressed genes (DEG), KEGG pathway enrichment, and gene ontology enrichment between treatments were determined based on the FDR-corrected P-value. Postruminal casein infusion downregulated (padj < 0.05) 7 genes of the jejunal mucosa and did not result in any enriched KEGG pathways or gene ontologies. Exogenous GLP-2 administration upregulated (padj < 0.05) 667 DEGs, 26 KEGG pathways, 198 biological processes, 56 cellular components, and 60 molecular functions. Exogenous GLP-2 downregulated (padj < 0.05) 1101 DEGs, 14 KEGG pathways, 270 biological processes, 105 cellular components, and 46 molecular functions. Enrichment analyses revealed that exogenous GLP-2 administration affected several pathways involving mucosal growth, nutrient digestion, absorption, and metabolism, and intestinal barrier function. Results of the current study identified pathways affected by exogenous GLP-2 administration that could have implications for improved animal growth and feed efficiency in cattle. This research generated novel targets for future research to elucidate mechanisms of GLP-2-mediated responses in the jejunal mucosa.
2023-11-21 | GSE248162 | GEO
Project description:We previously demonstrated that postruminal casein infusion and exogenous glucagon-like peptide 2 (GLP-2) administration independently stimulated growth and carbohydrase activity of the pancreas and jejunal mucosa in cattle. The objective of the current study was to profile the jejunal mucosal transcriptome of cattle using next-generation RNA sequencing in response to postruminal casein infusion and exogenous GLP-2. Twenty-four Holstein steers [250 ± 23.1 kg body weight (BW)] received a continuous abomasal infusion of 3.94 g raw corn starch/kg of BW combined with either 0 or 1.30 g casein/kg of BW for 7 d. Steers received subcutaneous injections at 0800 and 2000 h to provide either 0 or 100 μg GLP-2/kg of BW per day. At the end of the 7-d treatment period, steers were slaughtered for collection of the jejunal mucosa. Total RNA was extracted from jejunal mucosal tissue, strand-specific cDNA libraries were prepared, and RNA sequencing was conducted to generate 150-bp paired-end reads at a depth of 40 M reads per sample. Differentially expressed genes (DEG), KEGG pathway enrichment, and gene ontology enrichment were determined based on the FDR-corrected P-value (padj). Exogenous GLP-2 administration upregulated (padj < 0.05) 667 genes and downregulated 1,101 genes of the jejunal mucosa. Sphingolipid metabolism, bile secretion, adherens junction, and galactose metabolism were among the top KEGG pathways enriched with upregulated DEG (padj < 0.05) in response to exogenous GLP-2 administration. The top gene ontologies enriched with upregulated DEG (padj < 0.05) in response to exogenous GLP-2 administration included nutrient metabolic processes, brush border and bicellular tight junction assembly, and enzyme and transporter activities. Exogenous GLP-2 administration increased or tended to increase (padj < 0.10) brush border carbohydrase (MGAM, LCT, TREH), hexose transporter (SLC5A1, SLC2A2), and associated transcription factor (HNF1, GATA4, KAT2B) mRNA expression of the jejunal mucosa. Gene ontologies and KEGG pathways that were downregulated (padj < 0.05) in response to exogenous GLP-2 were related to genetic information processing. Postruminal casein infusion downregulated (padj < 0.05) 7 jejunal mucosal genes that collectively did not result in enriched KEGG pathways or gene ontologies. This study highlights some of the transcriptional mechanisms associated with increased growth, starch assimilation capacity, and barrier function of the jejunal mucosa in response to exogenous GLP-2 administration.
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Project description:Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal function. Wnt/beta-catenin signaling controls metabolic zonation by activating genes in the perivenous hepatocytes, while suppressing genes in the periportal counterparts. We now demonstrate that glucagon opposes the actions of Wnt/beta-catenin signaling on gene expression and metabolic zonation pattern. The effects were more pronounced in the periportal hepatocytes where 28% of all genes were activated by glucagon and inhibited by Wnt/beta-catenin. The glucagon and Wnt/beta-catenin receptors and their signaling pathways are uniformly distributed in periportal and perivenous hepatocytes and the expression is not regulated by the opposing signal. Collectively, our results show that glucagon controls gene expression and metabolic zonation in the liver through a counter play with the Wnt/beta-catenin signaling pathway.
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Project description:Alterations in intestinal microbiota and intestinal short chain fatty acids profiles have been associated with the pathophysiology of obesity and insulin resistance. Whether intestinal microbiota dysbiosis is a causative factor in humans remains to be clarified We examined the effect of fecal microbial infusion from lean donors on the intestinal microbiota composition, glucose metabolism and small intestinal gene expression. Male subjects with metabolic syndrome underwent bowel lavage and were randomised to allogenic (from male lean donors with BMI<23 kg/m2, n=9) or autologous (reinfusion of own feces, n=9) fecal microbial transplant. Insulin sensitivity and fecal short chain fatty acid harvest were measured at baseline and 6 weeks after infusion. Intestinal microbiota composition was determined in fecal samples and jejunal mucosal biopsies were also analyzed for the host transcriptional response. Insulin sensitivity significantly improved six weeks after allogenic fecal microbial infusion (median Rd: from 26.2 to 45.3 μmol/kg.min, p<0.05). Allogenic fecal microbial infusion increased the overall amount of intestinal butyrate producing microbiota and enhanced fecal harvest of butyrate. Moreover, the transcriptome analysis of jejunal mucosal samples revealed an increased expression of genes involved in a G-protein receptor signalling cascade and subsequently in glucose homeostasis. Lean donor microbial infusion improves insulin sensitivity and levels of butyrate-producing and other intestinal microbiota in subjects with the metabolic syndrome. We propose a model wherein these bacteria provide an attractive therapeutic target for insulin resistance in humans. (Netherlands Trial Register NTR1776).
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