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Dietary dimethylglycine sodium salt supplementation alleviates redox status imbalance and intestinal dysfunction in weaned piglets with Intrauterine growth restriction

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Animal Nutrition 2022年第3期10卷 188-197页

作者： Kaiwen Bai Luyi Jiang Qiming Li Jingfei Zhang Lili Zhang Tian Wang College of Animal Science and Technology Nanjing Agricultural UniversityNanjingChina College of Animal Science Zhejiang UniversityHangzhouChina

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(Pgrowth 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 proliferatoractivated receptorgcoactivator-1a(PG

关键词： Intrauterine growth restriction Weaned piglet Jejunum Redox status Mitochondrial function Dimethylglycine sodium salt

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Dietary N-carbamylglutamate or L-arginine improves fetal intestinal amino acid profiles during Intrauterine growth restriction in undernourished ewes

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Animal Nutrition 2022年第1期8卷 341-349页

作者： Hao Zhang Xiaoyun Liu Yi Zheng Ying Zhang Juan J.Loor Hongrong Wang Mengzhi Wang State Key Laboratory of Sheep Genetic Improvement and Healthy Production Xinjiang Academy of Agricultural and Reclamation ScienceShihezi 832000China Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition College of Animal Science and TechnologyYangzhou UniversityYangzhou 225009China Joint International Research Laboratory of Agriculture and Agri-Product Safety The Ministry of Education of ChinaYangzhou UniversityYangzhou 225009China Department of Animal Sciences and Division of Nutritional Sciences University of IllinoisUrbanaIL 61801USA

Our previous studies demonstrated that prenatal in utero growth restriction impairs postnatal intestinal function.Thus,improving postpartal intestinal absorption capacity and growth by manipulating the maternal diet prepartum is of importance.This work was conducted to determine whether supplementation of N-carbamylglutamate(NCG)or rumen-protected L-arginine(RP-Arg)increased fetal intestinal amino acid(AA)profiles in intrauterine growth retardation(IUGR)fetuses.On d 35 of gestation,Hu ewes(n=32)carrying twin fetuses were randomized into 4 groups(8 ewes and 16 fetuses in each group),where diets were as follows:100%of nutrient requirements recommended by National Research Council(NRC,2007)(CON);50%of nutrient requirements recommended by NRC(2007)(RES);RES+RPArg(20 g/d),(RES+ARG);and RES+NCG(5 g/d),(RES+NCG).On d 110 of gestation,both fetal and maternal tissues were collected and weighed.Compared with RES,solute carrier family 1,member 5(SLC1A5)was upregulated(Pgrowth and AA profiles independent of the fetal intestine.This would help demonstrate the relative contribution of intestinal uptake in fetal life.

关键词： Intrauterine growth restriction L-arginine Fetal sheep N-carbamylglutamate Intestinal amino acids

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Treatment of immune dysfunction in Intrauterine growth restriction piglets via supplementation with dimethylglycine sodium salt during the suckling period

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Animal Nutrition 2022年第4期11卷 215-227页

作者： Kaiwen Bai Luyi Jiang Tian Wang Wei Wang School of Biological and Chemical Engineering Zhejiang University of Science and TechnologyHangzhouChina Institute of Dairy Science Ministry of Education Key Laboratory of Molecular Animal NutritionCollege of Animal SciencesZhejiang UniversityHangzhouChina College of Animal Science and Technology Nanjing Agricultural UniversityNanjingChina

This study aimed to investigate the mechanism of small intestinal immune dysfunction in Intrauterine growth restriction(IUGR)newborn piglets and relieve this dysfunction via dimethylglycine sodium salt(DMG-Na)supplementation during the suckling period.Thirty sows(Duroc×[Landrace×Yorkshire])were selected,and 1 male newborn piglet with normal birth weight(NBW)and 1 male newborn piglet with IUGR were obtained from each sow.Among them,10 NBW and 10 IUGR newborns were euthanized without suckling.The other 20 NBW newborns were allocated to the group named NCON,which means NBW newborns fed a basic milk diet(BMD)(n=10),and the group named ND,which means NBW newborns fed BMD supplemented with 0.1%DMG-Na(n=10);the other 20 IUGR newborns were assigned to the group named ICON,which means IUGR newborns fed BMD(n=10),and the group named ID,which means IUGR newborns fed BMD supplemented with 0.1%DMG-Na(n=10).The newborns were fed BMD from 7 to 21 d of age and euthanized at 21 d of age to collect serum and small intestinal samples.The growth performance,small intestinal histological morphology and sub-organelle ultrastructure,serum immunoglobulin,small intestinal digestive enzyme activity,inflammatory cytokine level,and jejunum mRNA and protein expression of the toll-like receptor 4(TLR4)/nucleotide-binding oligomerization domain protein(NOD)/nuclear factor-k B(NF-k B)network deteriorated in the ICON group compared to that in the NCON group.The small intestinal histological morphology and suborganelle ultrastructure,serum immunoglobulin,small intestinal digestive enzyme activity,and inflammatory cytokine level improved(P<0.05)in the ID group compared to those in the ICON group.The jejunum mRNA and protein expression of the TLR4/NOD/NF-k B network improved(P<0.05)in the ID group compared to that in the ICON group.In conclusion,the activity of the TLR4/NOD/NF-k B pathway was inhibited in the IUGR newborns,which in turn led to their jejunum immune dysfunction and reduced their performance.By ingesting DMG-Na,the IUGR newborns activ

关键词： Intrauterine growth restriction Piglet Small intestine Immune dysfunction Dimethylglycine sodium salt

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Dietary rumen-protected L-arginine or N-carbamylglutamate attenuated fetal hepatic inflammation in undernourished ewes suffering from Intrauterine growth restriction

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Animal Nutrition 2021年第4期7卷 1095-1104页

作者： Hao Zhang Ying Zhang Yi Ma Mabrouk Elsabagh Hongrong Wang Mengzhi Wang State Key Laboratory of Sheep Genetic Improvement and Healthy Production Xinjiang Academy of Agricultural Reclamation SciencesShihezi832000China Joint International Research Laboratory of Agriculture and Agri-Product Safety The Ministry of Education of ChinaYangzhou UniversityYangzhou225009China Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition College of Animal Science and TechnologyYangzhou UniversityYangzhou225009China Department of Animal Production and Technology Faculty of Agricultural Sciences and TechnologiesNigde Omer Halisdemir UniversityNigde51240Turkey Department of Nutrition and Clinical Nutrition Faculty of Veterinary MedicineKafrelsheikh UniversityKafrelsheikh33516Egypt

This study aimed to explore whether dietary rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)supplementation to feed-restricted pregnant ewes counteracts fetal hepatic inflammation and innate immune dysfunction associated with intrauterine growth retardation(IUGR)in ovine fetuses.On d 35 of pregnancy,twin-bearing Hu ewes(n=32)were randomly assigned to 4 treatment groups(8 ewes and 16 fetuses per group)and fed diets containing 100%of the NRC requirements(CON),50%of the NRC requirements(RES),RES+RP-Arg(20 g/d)(RESA),or RES+NCG(5 g/d)(RESN).At 08:00 on d 110 of gestation,fetal blood and liver tissue samples were collected.The levels of triglyceride,free fatty acid,cholesterol andβ-hydroxybutyrate in the fetal blood of RESA and RESN groups were lower(Pgrowth factorβ(TGFβ),and nuclear factor kappa B(NF-κB)mRNA levels in the fetal liver were decreased(P<0.05)by the NCG or RP-Arg supplementation compared to the RES treatment.Similarly,the toll-like receptor(TLR)-4,MyD88,TGFβ,and p-c-Jun N-terminal kinase(JNK)protein levels in the fetal liver were reduced(P<0.05)in the NCG and RP-Arg-supplemented groups compared to the RES group.These results showed that dietary supplementation of RP-Arg or NCG to underfed pregnant ewes could protect against IUGR fetal hepatic inflammation via improving lipid metabolism,down-regulating the TLR-4 and the inflammatory JNK and NF-icB signaling pathways,and decreasing cytokine production in ovine fetal blood and liver tissue.

关键词： L-arginine Fetal sheep Liver inflammation Intrauterine growth restriction N-carbamylglutamate

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Intrauterine growth restriction alters growth performance, plasma hormones,and small intestinal microbial communities in growing-finishing pigs

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Journal of Animal Science and Biotechnology 2021年第1期12卷 340-357页

作者： Liang Xiong Jinming You Wanghong Zhang Qian Zhu Francois Blachier Yulong Yin Xiangfeng Kong CAS Key Laboratory of Agro-ecological Processes in Subtropical Regions Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125HunanChina Key Laboratory of Animal Nutrition in Jiangxi Province College of Animal Science and TechnologyJiangxi Agricultural UniversityNanchang 440000JiangxiChina UniversitéParis-Saclay AgroParisTechINRAEUMR PNCA75005 ParisFrance.

Background: The interaction of the gut microbiota with key metabolic and physiological processes may be associated with poor growth outcomes in animals born with Intrauterine growth restriction(IUGR).Results: growth performance, plasma hormone concentrations, and intestinal microbiota composition were analyzed in IUGR pigs and in normal birth weight(NBW) pigs when the NBW pigs reached 25, 50, and 100 kg of body weight(BW). Compared to NBW pigs, IUGR pigs had lower initial, weaned, and final BW, and lower average daily gain and average daily feed intake in all the considered time points. In the 25 kg BW group, IUGR pigs had higher concentrations of plasma ghrelin and pancreatic polypeptide(PP), but lower insulin concentration than NBW pigs, while the situation was reversed in the 50 kg BW group. As compared to NBW pigs, IUGR pigs had higher microbial alpha diversity in the jejunum and ileum;in the 50 and 100 kg BW groups, IUGR pigs had higher Firmicutes abundance but lower Proteobacteria abundance in the jejunum, and lower Lactobacillus abundance in the jejunum and ileum;in the 25 kg BW group, IUGR pigs showed higher unclassified Ruminococcaceae abundance in the ileum;and in 25 and 50 kg BW groups, IUGR pigs showed lower Ochrobactrum abundance in the jejunum.Spearman's correlation revealed that Lactobacillus was negatively correlated with growth performance, while unclassified Ruminococcaceae was positively correlated. Predictive metagenomic analysis detected significantly different expression of genes in the intestinal microbiota between IUGR and NBW pigs, suggesting different metabolic capabilities between the two groups.Conclusions: Growing-finishing IUGR pigs showed lower growth performance, higher microbial alpha diversity, and differences in plasma hormone concentrations compared to NBW pigs. Alterations in the abundance of Firmicutes,Proteobacteria, Ruminococcaceae, Lactobacillus, and Ochrobactrum in the small intestine may be associated with IUGR, and may therefore serve as a future target for gut microbio

关键词： Growing-finishing pigs growth performance Intrauterine growth restriction Microbial community Small intestine

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Antenatal taurine reduces cerebral cell apoptosis in fetal rats with Intrauterine growth restriction

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Neural Regeneration Research 2013年第23期8卷 2190-2197页

作者： Jing Liu Xiaofeng Wang Ying Liu Na Yang Jing Xu Xiaotun Ren Department of Neonatology and NICU of Bayi Children's Hospital General Hospital of Beijing Military Command

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of Intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with Intrauterine growth restriction, and neo- natal rats with Intrauterine growth restriction undergoing taurine supplement were obtained for fur- ther experiments. The terminal deoxyribonucleotidyl transferase （TdT）-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with Intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with Intrauterine growth restriction. Immu- nohistochemical staining revealed that taurine supplement increased glial cell line-derived neuro- trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

关键词： neural regeneration Intrauterine growth restriction fetal rats brain neural cells taurine cell apop-tosis glial cell line-derived neurotrophic factor caspase-3 neural development grants-supportedpaper neuroregeneration

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Embryonic Intrauterine growth restriction: report of two cases

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Chinese Medical Journal 2004年第11期117卷 1753-1755页

作者：李小毛沈慧敏史众杰 Department of Obstetrics and Gynecology Third Affiliated Hospital Sun Yat-sen University Guangzhou 510630

Foetal growth restriction (FGR), formerly named intrauterine growth retardation (IUGR), is very common clinically in late pregnancy. However, whether this phenomenon exists in early pregnancy has not been reported. We... 详细信息

关键词： embryo Intrauterine growth restriction earl y pregnancy

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Regulation of glucocorticoid-related genes and receptors/regulatory enzyme expression in Intrauterine growth restriction filial rats

Regulation of glucocorticoid-related genes and receptors/reg...

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第二十次全国儿科中西医结合学术会议

作者： Ying-xue Ding Ying Shi Wei-juan Han Hong Cui Department of Pediatrics Beijing Friendship HospitalCapital Medical University

Background:This study aims to explore factors that influence glucocorticoid(GC)-related genes and receptors/regulatory enzyme expression in Intrauterine growth restriction(IUGR) filial rats.Method:An IUGR animal model was established by starvation,and brain tissue was removed after birth.Affymetrix Rat Gene 2.0 ST microarray was used to screen different expressions of GC-related genesin IUGR brain tissues.The mRNA and protein levels of related genes were validated by RT-PCR and western blot.Results:Results of the microarray revealed that the expression of11β-Hsd2 was significantly downregulated in the IUGR groupcompared to the control group.Although Nr3 clexhibited an overexpression trend in the IUGR group,there were no significant differences between the two groups.Further analysis suggests that the 11β-Hsd2 was negatively correlated to Nr3 cl.In the transcription level,the expression level of 11β-Hsd2 mRNA decreased in the IUGR group,while the mRNA expression level of Nr3 cl significantly increased.In the protein level,the expression of 11β-Hsd2 significantly decreased in the IUGR group;while the expression of Nr3 cl significantly increased in the IUGR group.However,there were no significant differences in Nr3 clphosphorylated at S211 and S266 between the IUGR andcontrol groups.Conclusion:The expression of Nr3 cl was mainly regulatedby 11β-Hsd2,which could significantly inhibit its expression in IUGR rats.Phosphorylation on site S211 was the major activated form of Nr3 cl.We speculatethat IUGR brain damage was caused by excessive amounts of GC due to significantactivation by Nr3 cl.

关键词： Intrauterine growth restriction Glucocorticoid Glucocorticoid receptor 11β-hydroxysteroid dehydrogenase 2

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Supplemental Clostridium butyricum modulates lipid metabolism by reshaping the gut microbiota composition and bile acid profile in IUGR suckling piglets

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Journal of Animal Science and Biotechnology 2023年第3期14卷 1150-1166页

作者： Xin Zhang Yang Yun Zheng Lai Shuli Ji Ge Yu Zechen Xie Hao Zhang Xiang Zhong Tian Wang Lili Zhang College of Animal Science and Technology Nanjing Agricultural University210095 NanjingJiangsuChina

Background Intrauterine growth restriction(IUGR)can cause lipid disorders in infants and have long-term adverse effects on their growth and development.Clostridium butyricum(C.butyricum),a kind of emerging probiotics,has been reported to effectively attenuate lipid metabolism dysfunctions.Therefore,the objective of this study was to investigate the effects of C.butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets.Methods Sixteen IUGR and eight normal birth weight(NBW)neonatal male piglets were used in this study.From d 3to d 24,in addition to drinking milk,the eight NBW piglets(NBW-CON group,n=8)and eight IUGR piglets(IUGR-CON group,n=8)were given 10 mL sterile saline once a day,while the remaining IUGR piglets(IUGR-CB group,n=8)were orally administered C.butyricum at a dose of 2×108colony-forming units(CFU)/kg body weight(suspended in 10 mL sterile saline)at the same frequency.Results The IUGR-CON piglets exhibited restricted growth,impaired hepatic morphology,disordered lipid metabolism,increased abundance of opportunistic pathogens and altered ileum and liver bile acid(BA)profiles.However,C.butyricum supplementation reshaped the gut microbiota of the IUGR-CB piglets,characterized by a decreased abundance of opportunistic pathogens in the ileum,including Streptococcus and Enterococcus.The decrease in these bile salt hydrolase(BSH)-producing microbes increased the content of conjugated BAs,which could be transported to the liver and function as signaling molecules to activate liver X receptorα(LXRα)and farnesoid X receptor(FXR).This activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol.As a result,the growth performance and morphological structure of the liver improved in the IUGR piglets.Conclusion These results indicate that C.butyricum supplementation in IUGR suckling piglets could decrease the abundance of BSH-producing microbes(Streptococcus and

关键词： Bile acid Clostridium butyricum Gut microbiota Intrauterine growth restriction Lipid metabolism Suckling piglet

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Dietary N-carbamylglutamate or L-arginine supplementation improves hepatic energy status and mitochondrial function and inhibits the AMP-activated protein kinase-peroxisome proliferator- activated receptor γ coactivator-1α-transcription factor A pathway in intrauterine-growth-retarded suckling lambs

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Animal Nutrition 2021年第3期7卷 859-867页

作者： Hao Zhang Xiaoyun Liu Shengnan Ren Mabrouk Elsabagh Mengzhi Wang Hongrong Wang Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition College of Animal Science and TechnologyYangzhou UniversityYangzhou225009China Joint International Research Laboratory of Agriculture and Agri-Product Safety The Ministry of Education of ChinaYangzhou UniversityYangzhou225009China Department of Animal Production and Technologies Faculty of Agricultural Sciences and TechnologiesNigde Omer Halisdemir UniversityCampusNigde51240Turkey Department of Nutrition and Clinical Nutrition Faculty of Veterinary MedicineKafrelsheikh UniversityKafr El-SheikhEgypt

The objective of this study was to investigate the effects of dietary administration of L-arginine(Arg)or N-carbamylglutamate(NCG)on hepatic energy status and mitochondrial functions in suckling Hu lambs with intrauterine growth retardation(IUGR).Forty-eight newborn Hu lambs of 7 d old were allocated into 4 treatment groups of 12 lambs each,in triplicate with 4 lambs per replicate(2 males and 2 females)as follows:CON(lambs of normal birth weight,4.25±0.14 kg),IUGR(3.01±0.12 kg),IUGR+1%Arg(2.99±0.13 kg),or IUGR+0.1%NCG(3.03±0.11 kg).The experiment lasted for 21 d,until d 28 after birth,and all lambs were fed milk replacer as a basal diet.Compared with IUGR lambs,NCG or Arg administration increased(P<0.05)the adenosine triphosphate(ATP)level and the activities of com-plexes I/III/IV,isocitrate dehydrogenase and citrate synthase in the liver.Compared with CON lambs,the relative mRNA levels of adenosine monophosphate-activated protein kinaseα1(AMPKα1),peroxisome proliferator-activated receptorγcoactivator-1α(PGC1α)and transcription factor A(TFAM)were increased(P<0.05)in the liver of IUGR lambs,but were decreased(P<0.05)in the liver of NCG-or Arg-treated lambs compared with those in the IUGR lambs.Compared with IUGR lambs,NCG or Arg administration decreased(P<0.05)the total AMPKα(tAMPKα)-to-phosphorylated AMPKα(pAMPKα)ratio and the protein expression of PGC1αand TFAM.The results suggested that dietary Arg or NCG supplements improved hepatic energy status and mitochondrial function and inhibited the AMPK-PGC1α-TFAM pathway in IUGR suckling lambs.

关键词： L-Arginine Liver Intrauterine growth restriction Energy status Mitochondrial function N-carbamylglutamate

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