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Hepatic transcript profiling in early lactating dairy cows fed rumen-protected niacin during the transition from late pregnancy to lactation

ABSTRACT: In dairy cows, administration of high dosages of niacin (NA) was found to cause anti-lipolytic effects, which are mediated by the NA receptor hydroxyl-carboxylic acid receptor 2 (HCAR2) in white adipose tissue (WAT), and thereby to an altered hepatic lipid metabolism. However, almost no attention has been paid to possible direct effects of NA in cattle liver, despite showing that HCAR2 is expressed also in the liver of cattle and is even more abundant than in WAT. Due to this, we hypothesized that feeding of rumen-protected NA to dairy cows influences critical metabolic and/or signaling pathways in the liver through inducing changes in the hepatic transcriptome. In order to identify these pathways, we applied genome-wide transcript profiling in liver biopsies obtained at 1 wk postpartum (p.p.) from dairy cows of a recent study (Zeitz et al., 2018) which were fed a total mixed ration without (control group) or with rumen-protected NA from 21 d before calving until 3 wk p.p. Hepatic transcript profiling revealed that a total of 487 transcripts were differentially expressed [filter criteria fold change (FC) > 1.2 or FC < -1.2 and P < 0.05] in the liver at 1 wk p.p. between cows fed NA and control cows. Substantially more transcripts were down-regulated (n = 338), while only 149 transcripts were up-regulated by NA in the liver of cows. Gene set enrichment analysis (GSEA) for the up-regulated transcripts revealed that the most enriched gene ontology (GO) biological process terms were exclusively related to immune processes, such as leukocyte differentiation, immune system process, leukocyte differentiation, activation of immune response and acute inflammatory response. In line with this, the plasma concentration of the acute phase protein haptoglobin tended to be increased in dairy cows fed rumen-protected NA compared to control cows (P < 0.1). GSEA of the down-regulated transcripts showed that the most enriched biological process terms were related to metabolic processes, such as cellular metabolic process, small molecule metabolic process, lipid catabolic process, organic cyclic compound metabolic process, small molecule biosynthetic process and cellular lipid catabolic process. In conclusion, hepatic transcriptome analysis shows that rumen-protected NA induces genes which are involved mainly in immune processes including acute phase response and stress response in dairy cows at wk 1 p.p. These findings indicate that supplementation of rumen-protected NA to dairy cows in the periparturient period may induce or amplify the systemic inflammation-like condition which is typically observed in the liver of high-yielding dairy cows in the p.p. period.

ORGANISM(S): Bos taurus

PROVIDER: GSE116058 | GEO | 2018/06/21

REPOSITORIES: GEO

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Project description:While dietary phosphorus (P) deprivation extending from the dry period into early lactation impairs health and productivity of cows, restricting dietary P supply during the dry period not only appears to be innocuous but rather effectively mitigates hypocalcemia during the first wk of lactation. To investigate possible negative metabolic effects of P deprivation during the dry period, the present study tested the hypothesis that restarted dietary P supply during the dry period alters the liver transcriptome of dairy cows during the periparturient period. Thirty late-pregnant multiparous Holstein-Friesian dairy cows entering their 2nd, 3rd or 4th lactation were assigned to either a dry cow ration with low (LP, 0.16% P in DM) or adequate P content (AP, 0.35% in DM) during the last 4 wk of the dry period (n = 15/group). Liver transcriptomics, which was carried out in a subset of five 2nd parity cows of each group (n = 5), and determination of selected hormones and metabolites in blood of all cows, was performed approximately one wk before calving and on d 3 postpartum. Liver tissue specimens and blood samples were obtained by a micro-invasive biopsy technique from the right 10th intercostal space and puncture of a jugular vein, respectively. 175 hepatic transcripts were expressed differentially between LP vs. AP cows in late pregnancy, and 165 transcripts differed between LP vs. AP cows in early lactation (Fold change > 1.3 and < -1.3, P < 0.05). In late pregnancy, the enriched biological processes of the up-regulated and the down-regulated transcripts were mainly related to immune processes and signal transduction (P < 0.05), respectively. In early lactation, the enriched biological processes of the up-regulated and the down-regulated transcripts were involved in mineral transport and biotransformation (P < 0.05), respectively. The plasma concentrations of the hormones and acute phase proteins (progesterone, insulin-like growth factor 1, serum amyloid alpha, haptoglobin, and 17β-estradiol) determined were not affected by P supply. These results suggest that P deprivation during the dry period moderately affects the liver transcriptome of cows in late pregnancy and early lactation, and causes no effects on important plasma hormones and acute phase proteins indicating no obvious impairment of health or metabolism of the cows.

Project description:Background: The liver is central to most economically important metabolic processes in cattle. However, the changes in expression of genes that drive these processes remain incompletely characterised. RNA-seq is the new gold standard for whole transcriptome analysis but so far there are no reports of its application to analysis of differential gene expression in cattle liver. We used RNA-seq to study differences in expression profiles of hepatic genes and their associated pathways in individual cattle in either mild negative energy balance (MNEB) or severe negative energy balance (SNEB). NEB is an imbalance between energy intake and energy requirements for lactation and body maintenance. This aberrant metabolic state affects high-yielding dairy cows after calving and is of considerable economic importance because of its negative impact on fertility and health in dairy herds. Analysis of changes in hepatic gene expression in SNEB animals will increase our understanding of NEB and contribute to the development of strategies to circumvent it. Results: RNA-seq analysis was carried out on total RNA from liver from early post partum Holstein Friesian cows in MNEB (n=5) and SNEB (n=6). 12,833 genes were deemed to be expressed (>4 reads per gene per animal), 413 of which were shown to be statistically significantly differentially expressed (SDE) at a false discovery rate (FDR) of 0.1% and 200 of which were SDE (FDR of 0.1%) with a ≥2-fold change between MNEB and SNEB animals. GOseq/KEGG pathway analysis showed that SDE genes with ≥2- fold change were associated (P <0.05) with 9 KEGG pathways. Seven of these pathways were related to fatty acid metabolism and unexpectedly included ‘Steroid hormone biosynthesis’, a process which mainly occurs in the reproductive organs rather than the liver. Conclusions: RNA-seq analysis showed that the major changes at the level of transcription in the liver of SNEB cows were related to fat metabolism. 'Steroid hormone biosynthesis', a process that normally occurs in reproductive tissue, was significantly associated with changes in gene expression in the liver of SNEB cows. Changes in gene expression were found in this pathway that have not been previously been identified in SNEB cows. 11 liver RNA samples were analysed in total, 6 samples were from SNEB animals and 5 samples from MNEB animals

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Hepatic transcript profiling in early lactating dairy cows fed rumen-protected niacin during the transition from late pregnancy to lactation

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