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Supplementation of a grape seed and grape marc meal extract decreases activities of the oxidative stress-responsive transcription factors NF-?B and Nrf2 in the duodenal mucosa of pigs.

ABSTRACT: BACKGROUND: In pigs, enteric infections and the development of gut disorders such as diarrhoea are commonly observed, particularly after weaning. The present study investigated the hypothesis that feeding a grape seed and grape marc extract (GSGME) as a dietary supplement has the potential to suppress the inflammatory process in the small intestine of pigs by modulating the activities of NF-?B and Nrf2 due to its high content of flavonoids. METHODS: Twenty-four crossbred, 6 weeks old pigs were randomly assigned to 2 groups of 12 animals each and fed nutritionally adequate diets without or with 1% GSGME for 4 weeks. RESULTS: Pigs administered GSGME had a lower transactivation of NF-?B and Nrf2 and a lower expression of various target genes of these transcription factors in the duodenal mucosa than control pigs (P < 0.05). Concentrations of ?-tocopherol and thiobarbituric acid reactive substances (TBARS) in liver and plasma and total antioxidant capacity of plasma and relative mRNA abundances of NF-?B and Nrf2 target genes in the liver did not differ between the two groups. However, the ratio of villus height:crypt depth and the gain:feed ratio was higher in the pigs fed GSGME than in control pigs (P < 0.05). CONCLUSIONS: This study shows that dietary supplementation of a polyphenol rich GSGME suppresses the activity of NF-?B in the duodenal mucosa of pigs and thus might provide a useful dietary strategy to inhibit inflammation in the gut frequently occurring in pigs. Feeding GSGME did not influence vitamin E status and the antioxidant system of the pigs but improved the gain:feed ratio. In overall, the study suggests that polyphenol-rich plant extracts such GSGME could be useful feed supplements in pig nutrition, in order to maintain animal health and improve performance.

SUBMITTER: Gessner DK

PROVIDER: S-EPMC3599961 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Supplementation of a grape seed and grape marc meal extract decreases activities of the oxidative stress-responsive transcription factors NF-κB and Nrf2 in the duodenal mucosa of pigs.

Gessner Denise K DK Fiesel Anja A Most Erika E Dinges Jennifer J Wen Gaiping G Ringseis Robert R Eder Klaus K

Acta veterinaria Scandinavica 20130302

<h4>Background</h4>In pigs, enteric infections and the development of gut disorders such as diarrhoea are commonly observed, particularly after weaning. The present study investigated the hypothesis that feeding a grape seed and grape marc extract (GSGME) as a dietary supplement has the potential to suppress the inflammatory process in the small intestine of pigs by modulating the activities of NF-κB and Nrf2 due to its high content of flavonoids.<h4>Methods</h4>Twenty-four crossbred, 6 weeks ol ...[more]

PMID: 23453040

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Project description: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.

Project description:As polyphenols are exerting a broad spectrum of metabolic effects, we hypothesize that feeding of GSGME might influence other metabolic pathways in the liver which could account for the positive effects of GSGME observed in cows during early lactation. In order to investigate this hypothesis, we used using a genome-wide transcript profiling technique to explore changes in the hepatic transcriptome of cows supplemented with GSGME during the transition period. Transcriptomic analysis of the liver revealed 207 differentially expressed transcripts (fold change > 1.3 or < -1.3, P < 0.05), from which 156 (155 mRNAs, 1 miRNA) were up- and 51 (43 mRNAs, 8 miRNAs) 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, such as M phase, cell cycle phase, mitotic cell phase and microtubule cytoskeleton and the most enriched KEGG database pathways were p53 signaling and cell cycle. Functional analysis of the 43 down-regulated mRNAs revealed that 13 genes (XBP1, HSPA5, HERPUD1, DNAJC5G, CALR, PDIA4, DNAJB11, PHLDA1, PPP1R3C, GADD45B, BAG3, HYOU1, MANF) are involved in ER stress-induced UPR. Moreover, several of the down-regulated mRNAs, like CXCL14 and CCL3L1L and the acute phase protein SAA4, play an important role in inflammatory processes. Accordingly, protein folding, response to unfolded protein, response to protein stimulus, unfolded protein binding, chemokine activity, chemokine receptor binding 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 SAA and haptoglobin were reduced in cows fed GSGME compared to control cows. Collectively, our findings from transcriptome analysis of down-regulated mRNAs and functional analysis of mRNAs targeted by the up-regulated mir-376c clearly indicate that GSGME is able to inhibit inflammatory processes and ER stress in the liver of dairy cows during early lactation. Moreover, our findings indicate that at least some of the GSGME effects on the hepatic transcriptome of dairy cows are mediated by miRNA-mRNA interactions.

Project description:Genetic selection in parental broiler breeders has increased their susceptibility to metabolic disorders and reproductive dysfunction. We have recently shown that maternal dietary grape seed extract (GSE) supplementation in hens improves fertility parameters, egg quality, oxidative stress in different tissues and the quality of F1 chicks. Here, we analysed the growth and fertility (both female and male) of the F1 generation animals and the quality of their offspring (F2 generation). Eggs issued from hens supplemented with GSE presented lower ROS production than control hens, suggesting a change in the embryonic environment. However, this did not affect the growth nor the body composition of male and female F1s from hatching to adulthood (37 weeks of age). At 37 weeks of age, the biochemistry analysis of the GSE-F1 muscle has revealed an increase in sensitivity to oxidative stress and a slight change in lipid composition. Both male and female F1-GSE groups presented a delay in puberty with a lower testis volume at 30 weeks of age and lower ovary development at 26 weeks of age. Adult GSE-F1 males did not present histological alterations of seminiferous tubules or semen production, but the semen quality was degraded due to higher oxidative stress and DNA-damaged spermatozoa compared with control F1 animals. In adult GSE-F1 females, despite the delay in puberty, the females laid more eggs of better quality (fewer broken eggs and a higher hatching rate). At hatching, the weight of the chicks from GSE-F1 females was reduced, and this effect was stronger in F2 male chicks (F2) compared with F2 control chicks (F2), because of the lower muscle volume. In conclusion, we can raise the hypothesis that maternal dietary GSE supplementation produces eggs with change in embryonic metabolism, which may affect in adulthood the fertility. The data obtained from the F1-GSE group pointed to a sex-specific modification with higher egg quality in females but semen sensitive to stress in males. Finally, male F2 chicks were leaner than control chicks. Thus, maternal dietary grape seed extract (GSE) supplementation in hens may impact on the fertility of the offspring in a sex-specific manner in subsequent generations.

Dataset Information

Supplementation of a grape seed and grape marc meal extract decreases activities of the oxidative stress-responsive transcription factors NF-?B and Nrf2 in the duodenal mucosa of pigs.

Publications

Supplementation of a grape seed and grape marc meal extract decreases activities of the oxidative stress-responsive transcription factors NF-κB and Nrf2 in the duodenal mucosa of pigs.

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