Dimethylglycine Sodium Salt Alleviates Intrauterine Growth Restriction-Induced Low Growth Performance, Redox Status Imbalance, and Hepatic Mitochondrial Dysfunction in Suckling Piglets.
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ABSTRACT:
SUBMITTER: Bai K
PROVIDER: S-EPMC9263627 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There are few studies on the mechanism of redox status imbalance and intestinal dysfunction in intrauterine growth restricted (IUGR) newborn piglets. Here, we investigated the mechanism of jejunum dysfunction in weaned piglets with IUGR and the mechanism through which dimethylglycine sodium salt (DMG-Na) supplementation improving the imbalance of their redox status. In this work, a total of 10 normal birth weight (NBW) newborn piglets and 20 IUGR newborn piglets were obtained. After weaning at 21 d, they were assigned to 3 groups (n = 10/group): NBW weaned piglets fed standard basal diets (NBWC); one IUGR weaned piglets fed standard basal diets (IUGRC); another IUGR weaned piglets from the same litter fed standard basal diets plus 0.1% DMG-Na (IUGRD). The piglets in these 3 groups were sacrificed at 49 d of age, and the blood and jejunum samples were collected immediately. The growth performance values in the IUGRC group were lower (P < 0.05) than those in the NBWC group. Jejunum histomorphological parameters, inflammatory cytokines, and digestive enzyme activity as well as serum immunoglobulin were lower (P < 0.05) in the IUGRC group than those in the NBWC group. Compared with these in the NBWC group, the redox status of serum, jejunum, and mitochondria and the expression levels of jejunum redox status-related, cell adhesion-related, and mitochondrial function-related genes and proteins were suppressed in the IUGRC group (P < 0.05). However, compared with those in the IUGRC group, the growth performance values, jejunum histomorphological parameters, inflammatory cytokines, digestive enzyme activity, serum immunoglobulin, redox status of serum, jejunum, and mitochondria, and the expression levels of jejunum redox status-related, cell adhesion-related, and mitochondrial function-related genes and proteins were improved (P < 0.05) in the IUGRD group. In conclusion, dietary DMG-Na supplementation alleviates redox status imbalance and intestinal dysfunction in IUGR weaned piglets mainly by activating the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptorγcoactivator-1α (PGC1α) pathway, thereby improving their unfavorable body state.
| S-EPMC9207221 | biostudies-literature
Project description:The present study used intrauterine growth restriction (IUGR) piglets as an animal model to determine the effect of Bacillus subtilis on intestinal integrity, antioxidant capacity, and microbiota in the jejunum of suckling piglets. In total, 8 normal birth weight (NBW) newborn piglets (1.62 ± 0.10 kg) and 16 newborn IUGR piglets (0.90 ± 0.08 kg) were selected and assigned to three groups. Piglets were orally gavaged with 10-mL sterile saline (NBW and IUGR groups), and IUGR piglets were orally gavaged with 10-mL/d bacterial fluid (B. subtilis diluted in sterile saline, gavage in the dose of 2 × 109 colony-forming units per kg of body weight; IBS group; n = 8). IUGR induced jejunal barrier dysfunction and redox status imbalance of piglets, and changed the abundances of bacteria in the jejunum. Treatment with B. subtilis increased (P < 0.05) the ratio of villus height to crypt depth (VH/CD) in the jejunum, decreased (P < 0.05) the plasma diamine oxidase (DAO) activity, and enhanced (P < 0.05) the gene expressions of zonula occludens-1 (ZO-1), occludin, and claudin-1 in the jejunum of IUGR piglets. Treatment with B. subtilis decreased (P < 0.05) the concentration of protein carbonyl (PC) and increased (P < 0.05) the activities of catalase (CAT) and total superoxide dismutase (T-SOD) in the jejunum of IUGR piglets. Treatment with B. subtilis also increased (P < 0.05) gene expressions of superoxide dismutase 1 (SOD1), CAT, and nuclear factor erythroid 2-related factor (Nrf2), as well as the protein expressions of heme oxygenase-1 (HO-1), SOD1, and Nrf2 in the jejunum of IUGR piglets. Treatment with B. subtilis also improved the abundances and the community structure of bacteria in the jejunum of IUGR piglets. These results suggested that IUGR damaged the jejunal barrier function and antioxidant capacity of suckling piglets, and altered the abundances of bacteria in the jejunum. Treatment with B. subtilis improved the intestinal integrity and antioxidant capacity while also improved the abundances and structure of bacteria in the jejunum of suckling piglets.
| S-EPMC8493892 | biostudies-literature
Project description:Intrauterine growth restriction (IUGR) impairs fetal growth and development, perturbs nutrient metabolism, and increases the risk of developing diseases in the postnatal life. However, the underlying mechanisms by which IUGR affects fetuses remain incompletely understood. Here, we applied high-throughput proteomics approach and biochemical analysis to investigate the impact of IUGR on fetal liver.
2016-03-15 | PXD003524 | Pride
Project description:Emerging knowledge shows the importance of early life events in programming the intestinal mucosal immune system and development of the intestinal barrier function. These processes depend heavily on close interactions between gut microbiota and host cells in the intestinal mucosa. In turn, development of the intestinal microbiota is largely dependent on available nutrients and substrates required for the specific microbial community structures to expand. It is currently not known what the specificities are of intestinal microbial community structures in relation to the programming of the intestinal mucosal immune system and development of the intestinal barrier function. The objective of the present study was to investigate the effect of a nutritional intervention on intestinal development of suckling piglets by daily oral administration of fructooligosaccharides (FOS) over a period of 12 days. At the microbiota community level a clear “bifidogenic” effect of the FOS administration was observed in colon digesta at day 14. The former, however, did not translate into significant changes of local gene expression in the colonic mucosa. In the jejunum, significant changes were observed for microbiota composition at day 14, and microbiota diversity at day 25. In addition, significant differentially expressed gene sets in mucosal tissues of jejunum were identified at both days 14 and 25 of age. At the age of 14 days, lower activity of cell cycle-related processes and a higher activity of extracellular matrix processes were observed in jejunal scrapings of piglets supplemented with FOS compared to control piglets. At day 25, lower activity of immune-related processes in jejunal tissue were seen in piglets supplemented with FOS. Histological parameters, villi height and crypt depth, were significantly different at day 25 between the experimental and control group, where piglets supplemented with FOS had higher villi and deeper crypts. We conclude that oral FOS administration during the suckling period of piglets has significant bifidogenic effects on the microbiota in the colon and on gene expression in jejunal mucosa scrapings. We hypothesize that FOS supplementation of suckling piglets results in a higher butyrate production in the colon due to the increase in bifidobacteria and lactobacilli in the hindgut. We further speculate that a higher butyrate production in colonic digesta relates to changes in gene expression in the jejunum by thus far unknown mechanisms.
2018-01-29 | GSE101147 | GEO
Project description:AimIntrauterine growth retardation (IUGR) is a prevalent problem in mammals. The present study was conducted to unveil the alterations in intestinal microbiota in IUGR piglets.Methods and resultsWe identified the alterations of small intestinal microbiota in IUGR piglets on 7, 21 and 28 days of age using 16S rRNA sequencing. The results showed that IUGR piglets had a decreased alpha diversity of jejunum microbiota at 7 and 21 days of age; had lower abundances of Bacteroidetes and Bacteroides in the jejunum at 7, 21 and 28 days of age, Oscillibacter in the jejunum at 21 days of age, and Firmicutes in the ileum at 21 days of age; whereas they had higher abundances of Proteobacteria and Pasteurella in the ileum at 21 days of age and Escherichia-Shigella in the jejunum at 28 days of age. Correlation analysis showed that Bacteroides, Oscillibacter and Ruminococcaceae_UCG-002 compositions were positively associated with the body weight (BW) of IUGR piglets, nevertheless Proteobacteria and Escherichia-Shigella relative abundances were negatively correlated with the BW of IUGR piglets. Gene function prediction analysis indicated that microbiota-associated carbohydrate metabolism, lipid metabolism, glycan biosynthesis and metabolism, amino acid metabolism, and xenobiotics biodegradation and metabolism were downregulated in the IUGR piglets compared to control piglets.ConclusionsThe present study profiled the intestinal microbiota of newborn piglets with IUGR and the newborn IUGR piglets have lower diversity and different taxonomic abundances. Alterations in the abundances of Bacteroidetes, Bacteroides, Proteobacteria Escherichia-Shigella and Pasteurella may be involved in nutrient digestion and absorption, as well as the potential mechanisms connecting to the growth and development of IUGR in mammals.Significance and impact of the studyThe small intestinal microbiota were highly shaped in the IUGR piglets, which might further mediate the growth and development of IUGR piglets; and the gut microbiota could serve as a potential target for IUGR treatment.
| S-EPMC6916403 | biostudies-literature
Project description:Transcriptional profiling of 25d old piglets comparing control untreated suckling jejunum with weaned piglets' jejunum. The goal was to gain new insight into the interaction between weaning and intestinal function.A keen interest is paid in deciphering expression changes of apoptosis or cell cycle control genes. The statistical analysis of gene ontology revealed that most of these altered genes are metabolic-related enzymes and regulators which may involved in the biological regulation, developmental process, and cellular process. Weaning also causes alterations in various immune response pathways. Results likely indicate that weaning induced cell cycle arrest, enhanced apoptosis, and inhibited cell proliferation.
2014-05-01 | GSE48050 | GEO
Project description:Impaired intestinal function is frequently detected in newborns with intrauterine growth restriction (IUGR), whereas the mechanism between transcriptome profiles and small intestinal dysfunction is still unclear. Therefore, this study was conducted by using IUGR neonatal piglets to uncover the mechanism underlying intestinal dysfunction. Neonatal piglets with IUGR and normal birth weight (NBW) were sacrificed at birth. Transcriptomic sequencing was performed on jejunum samples and generated 18,997 and 17,531 genes in NBW and IUGR groups, respectively. A total of 10 differentially expressed genes (DEGs) were identified; of note, only seven were mapped to the genome reference database, with two up-regulated (HSF4 and NR1H4; heat shock transcription factor 4 and nuclear receptor subfamily 1 group H member 4, respectively) and five down-regulated (SLC35C1, BTNL3, BPI, NLRP6, and SLC5A8; Solute carrier family 35 member C1, butyrophilin like 3, bactericidal permeability increasing protein, NLR family pyrin domain containing 6, and solute carrier family 5 member 8, respectively). Combining an enrichment analysis and reverse transcriptase-quantitative polymerase chain reaction validation of DEGs, our results proved the lipid metabolism disorder, intestinal dysfunction, and inflammatory response in IUGR piglets. Here, IUGR piglets presented lower concentration of glucose and triglyceride and higher concentration of total cholesterol and low-density lipoprotein cholesterol in plasma, compared with NBW piglets. Histological analysis revealed decreased mucins and increased apoptosis in both jejunum and ileum for IUGR piglets. Collectively, we found that IUGR induced intestinal dysfunction by altering lipid metabolism, intestinal barrier, and inflammatory response in neonatal piglets at birth, which provides new insights into the prevention and treatment of IUGR that protects against metabolic disorders and inflammatory-related diseases.
| S-EPMC7324767 | biostudies-literature
Project description:Transcriptional profiling of 25d old piglets comparing control untreated suckling jejunum with weaned piglets' jejunum. The goal was to gain new insight into the interaction between weaning and intestinal function.A keen interest is paid in deciphering expression changes of apoptosis or cell cycle control genes. The statistical analysis of gene ontology revealed that most of these altered genes are metabolic-related enzymes and regulators which may involved in the biological regulation, developmental process, and cellular process. Weaning also causes alterations in various immune response pathways. Results likely indicate that weaning induced cell cycle arrest, enhanced apoptosis, and inhibited cell proliferation. Two-condition experiment, suckling control piglets' jejunum vs. weaned piglets' jejunum. Biological replicates: 4 control replicates, 4 weaned replicates.
2014-05-01 | E-GEOD-48050 | biostudies-arrayexpress
Project description:Dimethylglycine sodium salt (DMG-Na) has exhibited excellent advantages in animal experiments and human health. The present study aimed to investigate the effects of dietary supplementation with 0.1% DMG-Na on the growth performance, hepatic antioxidant capacity, and mRNA expression of mitochondria-related genes in low birth weight (LBW) piglets during weaning period. Sixteen piglets with normal birth weight (NBW) and 16 LBW piglets were fed either a basal diet or a 0.1% DMG-Na supplemented diet from age of 21 to 49 d. Blood and liver samples were collected at the end of the study. The results showed that compared with NBW piglets, LBW piglets exhibited greater (P < 0.05) alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase activities in the serum. LBW decreased (P < 0.05) the activity of glutathione peroxidase and increased (P < 0.05) the contents of malondialdehyde and H2O2 in liver. DMG-Na supplementation increased (P < 0.05) body weight gain, feed intake, and feed efficiency, decreased (P < 0.05) ALT and AST activities, and reduced the content of H2O2 in LBW piglets. LBW piglets had downregulated (P < 0.05) mRNA expression of thioredoxin 2, thioredoxin reductases 2, and nuclear respiratory factor-1 (Nrf1) in the liver. However, DMG-Na supplementation increased (P < 0.05) mRNA expression of Nrf1 in the liver. In conclusion, DMG-Na supplementation has beneficial effects in alleviating LBW-induced hepatic oxidative damage and changed mitochondrial genes expression levels, which is associated with increased antioxidant enzyme activities and up-regulating mRNA gene abundance.
| S-EPMC6127790 | biostudies-literature
Project description:Intrauterine growth restriction leads to the development of adult onset obesity/metabolic syndrome, diabetes mellitus, cardiovascular disease, hypertension, stroke, dyslipidemia, and non-alcoholic fatty liver disease/steatohepatitis. Continued postnatal growth restriction has been shown to ameliorate many of these sequelae. To further our understanding of the mechanism of how intrauterine and early postnatal growth affects adult health we have employed Affymetrix microarray-based expression profiling to characterize hepatic gene expression of male offspring in a rat model of maternal nutrient restriction in early and late life. At day 21 of life (p21) combined intrauterine and postnatal calorie restriction treatment led to expression changes in circadian, metabolic, and insulin-like growth factor genes as part of a larger transcriptional response that encompasses 144 genes. Independent and controlled experiments at p21 confirm the early life circadian, metabolic, and growth factor perturbations. In contrast to the p21 transcriptional response, at day 450 of life (d450) only seven genes, largely uncharacterized, were differentially expressed. This lack of a transcriptional response identifies non-transcriptional mechanisms mediating the adult sequelae of intrauterine growth restriction. Independent experiments at d450 identify a circadian defect as well as validate expression changes to four of the genes identified by the microarray screen which have a novel association with growth restriction. Emerging from this rich dataset is a portrait of how the liver responds to growth restriction through circadian dysregulation, energy/substrate management, and growth factor modulation.
| S-EPMC4565187 | biostudies-literature