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Bovine granulocytes gene expression profiles reflect the aberration of liver functions

ABSTRACT: Liver takes multifunctional important roles and the prediction of its function is hard issue. Detecting methods of gene expression profiles like microarray provide functional information of tissues. Liver and peripheral white blood cells (PBLs) were collected from two different feeding conditioned Holstein cows; estrus cycle and middle of gestation. Also PBLs were fractionated with gradient cells separation. The RNA was applied to oligo-microarray and qRT-PCR. It revealed a group of stable bovine liver genes in constant physiological feeding condition. When they applied to different cows fed in different status, the profiles of some specific genes in liver coincided with those in PBLs. Microarray data were applied to a principal component analysis (PCA). It was found that the liver gene expression profiles were more coincided those in granulocytes than other PBLs fraction by PCA. The relationship between gene profiles in liver and granulocytes was confirmed by qRT-PCR and Hierarchical cluster analysis. Granulocytes gene profile is more reliable than those in mononuclear cells in reflection of liver metabolic function. These results suggest that expressed genes in PBLs, especially granulocytes, may be convenient bio-indicators for diagnosis of clinical disorder and/or detecting aberration of liver function in different feeding condition of cows.

ORGANISM(S): Bos taurus

PROVIDER: GSE98018 | GEO | 2017/04/21

SECONDARY ACCESSION(S): PRJNA383674

REPOSITORIES: GEO

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Project description: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.

Project description:A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the transition period. Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 wk preceding calving (75 and 125% of estimated requirements). Liver samples were obtained at -7, 7, and 28 d relative to parturition and subsequent RNA was hybridized to the Agilent 44K Bovine (V2) Microarray chip. The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis. The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance indicated that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. Altered carbohydrate and amino acid metabolism indicated a greater and more prolonged negative energy balance post-calving in BCS5 cows overfed prepartum. This was indicated by opposite effects of pre-calving feeding in in BCS4 compared with BCS5 cows in amino acid, vitamin, and co-factor metabolism. The prepartum feed restriction ameliorated the metabolic adaptation to the new lactation in BCS5 cows, while detrimentally affecting BCS4 cows, which seemed to adapt better when overfed. Moreover, alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 cows and overfed BCS4 animals. IPA network analysis indicated liver damage in feed-restricted thin cows, likely due to metabolic overload. Overall, the data indicate that overfeeding in late-pregnancy should be limited to underconditioned animals, while cow with optimal degree of body condition should be maintained on an energy restricted diet.

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Bovine granulocytes gene expression profiles reflect the aberration of liver functions

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