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BMC Genomics

, 18:253

Non-human and non-rodent vertebrate genomics


BackgroundIt was recently reported that dairy cows fed a polyphenol-rich grape seed and grape marc meal extract GSGME during the transition period had an increased milk yield, but the underlying reasons remained unclear. As polyphenols exert a broad spectrum of metabolic effects, we hypothesized that feeding of GSGME influences metabolic pathways in the liver which could account for the positive effects of GSGME in dairy cows. In order to identify these pathways, we performed genome-wide transcript profiling in the liver and lipid profiling in plasma of dairy cows fed GSGME during the transition period at 1 week postpartum.

ResultsTranscriptomic analysis of the liver revealed 207 differentially expressed transcripts, from which 156 were up- and 51 were down-regulated, between cows fed GSGME and control cows. Gene set enrichment analysis of the 155 up-regulated mRNAs showed that the most enriched gene ontology GO biological process terms were dealing with cell cycle regulation and the most enriched Kyoto Encyclopedia of Genes and Genomes pathways were p53 signaling and cell cycle. Functional analysis of the 43 down-regulated mRNAs revealed that a great part of these genes are involved in endoplasmic reticulum ER stress-induced unfolded protein response UPR and inflammatory processes. Accordingly, protein folding, response to unfolded protein, unfolded protein binding, chemokine activity and heat shock protein binding were identified as one of the most enriched GO biological process and molecular function terms assigned to the down-regulated genes. In line with the transcriptomics data the plasma concentrations of the acute phase proteins serum amyloid A SAA and haptoglobin were reduced in cows fed GSGME compared to control cows. Lipidomic analysis of plasma revealed no differences in the concentrations of individual species of major and minor lipid classes between cows fed GSGME and control cows.

ConclusionsAnalysis of hepatic transcript profile in cows fed GSGME during the transition period at 1 week postpartum indicates that polyphenol-rich feed components are able to inhibit ER stress-induced UPR and inflammatory processes, both of which are considered to contribute to liver-associated diseases and to impair milk performance in dairy cows, in the liver of dairy cows during early lactation.

KeywordsTranscriptomics Lipidomics Dairy cow Early lactation Liver Polyphenols Grape seed and grape marc meal extract Endoplasmic reticulum stress Inflammation AbbreviationsAPPAcute phase protein

ATF6Activating trascription factor 6 ATF6

BAG3BCL2-associated anthanogene 3

BAK1BCL2 antagonist-killer 1

BAXBCL2 associated X, apoptosis regulator


BUB1BBUB1B mitotic checkpoint serine-threonine kinase B


CASP3Caspase 3

CCL3L1C-C motif chemokine ligand 3 like 1

CCNA2Cyclin A2

CDKN3Cyclin dependent kinase inhibitor 3

cDNAComplementary DNA

CECholesteryl esters

CENPACentromere protein A


CHOPC-EBP homologous transcription factor protein

CKAP2Cytoskeleton associated protein 2

CMC4C-X9-C motif containing 4

CPCrude protein

cRNAComplementary RNA

CVCoefficient of variability

CXCL14Chemokine ligand 14

DAVIDDatabase for Annotation, Visualization and Integrated Discovery

DDIT3DNA damage inducible transcript 3 DDIT3

DEPDC1DEP domain containing 1

DMIDry matter intake

DNAJB11DnaJ Hsp40 homolog, subfamily B, member 11

DNAJC5GDnaJ Hsp40 homolog, subfamily C, member 5G

ECT2Epithelial cell transforming 2

EDEM1ER degradation enhancing alpha-mannosidase-like protein 1

EIF2AEukaryotic translation initiation factor 2A

EREndoplasmic reticulum

ERADER-associated degradation

ERSEEndoplasmic reticulum stress elements

ESI-MS-MSelectrospray ionization tandem mass spectrometry


FCFree cholesterol

FDRFalse discovery rates

FGF-21Fibroblast-growth factor-21

GADD45BGrowth arrest and DNA damage inducible beta

GAS2L3Growth arrest specific 2 like 3

GEOGene expression omnibus

GOGene ontology

GSEAGene set enrichment analysis

GSGMEGrape seed and grape marc meal extract

HERPUD1Homocysteine inducible ER protein with ubiquitin like domain 1



HSPA5Heat shock 70 kDa protein 5

HYOU1Hypoxia up-regulated 1 HYOU1


KEGGKyoto encyclopedia of genes and genomes

KFBCentre of excellence for fluorescent bioanalytics

KIF11Kinesin family member 11


MANFMesencephalic astrocyte-derived neurotrophic factor

NENet energy

NEBNegative energy balance

NEFANon-esterified fatty acids

NF-κBNuclear factor kappa B

NUF2NDC80 kinetochore complex component


PDIA4Protein disulfide isomerase family A, member 4


PE-PPE-based plasmalogens

PERKProtein kinase RNA-like endoplasmic reticulum kinase

PHLDA1Pleckstrin homology-like domain, family A, member 1


PPP1R3CProtein phosphatase 1 regulatory subunit 3C

qPCRQuantitative real-time polymerase chain reaction

RINRNA integrity number

RMARobust multichip analysis

SAASerum amyloid A


SMC4Structural maintenance of chromosomes 4

SPC25SPC25 NDC80 kinetochore complex component SPC25


STMN1Stathmin 1


TMRTotal mixed ration

TPO2ATopoisomerase DNA II alpha


UPRUnfolded protein response

WARSTryptophanyl-tRNA synthetase

XBP1X-box binding protein 1

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-017-3638-1 contains supplementary material, which is available to authorized users.

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Autor: Denise K. Gessner - Anne Winkler - Christian Koch - Georg Dusel - Gerhard Liebisch - Robert Ringseis - Klaus Eder


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