Background Intrauterine growth retardation(IUGR)is one of the major constraints in animal production.Our previ-ous study showed that piglets with IUGR are associated with abnormal bile acid(BA)metabolism.This study ex...Background Intrauterine growth retardation(IUGR)is one of the major constraints in animal production.Our previ-ous study showed that piglets with IUGR are associated with abnormal bile acid(BA)metabolism.This study explored whether dietary BA supplementation could improve growth performance and colonic development,function,micro-biota,and metabolites in the normal birth weight(NBW)and IUGR piglets.A total of 48 weaned piglets(24 IUGR and 24 NBW)were allocated to four groups(12 piglets per group):(i)NBW group,(ii)NBW+BA group,(iii)IUGR group,and(iv)IUGR+BA group.Samples were collected after 28 days of feeding.Results The results showed that dietary BA supplementation increased the length and weight of the colon and colon weight to body weight ratio,while decreased the plasma diamine oxidase(DAO)concentration in the NBW pig-lets(P<0.05).Dietary BA supplementation to IUGR piglets decreased(P<0.05)the plasma concentrations of D-lactate and endotoxin and colonic DAO and endotoxin,suggesting a beneficial effect on epithelial integrity.Moreover,dietary BA supplementation to NBW and IUGR piglets increased Firmicutes abundance and decreased Bacteroidetes abundance(P<0.05),whereas Lactobacillus was the dominant genus in the colon.Metabolome analysis revealed 65 and 51 differential metabolites in the colon of piglets fed a diet with/without BA,respectively,which was associated with the colonic function of IUGR piglets.Furthermore,dietary BA supplementation to IUGR piglets upregulated the expressions of CAT,GPX,SOD,Nrf1,IL-2,and IFN-γin colonic mucosa(P<0.05).Conclusions Collectively,dietary BA supplementation could improve the colonic function of IUGR piglets,which was associated with increasing proportions of potentially beneficial bacteria and metabolites.Furthermore,BA shows a promising application prospect in improving the intestinal ecosystem and health of animals.展开更多
Background:Endoplasmic reticulum(ER)stress and autophagy are implicated in the pathophysiology of intestinal inflammation;however,their roles in intrauterine growth retardation(IUGR)-induced colon inflammation are unc...Background:Endoplasmic reticulum(ER)stress and autophagy are implicated in the pathophysiology of intestinal inflammation;however,their roles in intrauterine growth retardation(IUGR)-induced colon inflammation are unclear.This study explored the protective effects of natural stilbene pterostilbene on colon inflammation using the IUGR piglets and the tumor necrosis factor alpha(TNF-α)-treated human colonic epithelial cells(Caco-2)by targeting ER stress and autophagy.Results:Both the IUGR colon and the TNF-α-treated Caco-2 cells exhibited inflammatory responses,ER stress,and impaired autophagic flux(P<0.05).The ER stress inducer tunicamycin and the autophagy inhibitor 3-methyladenine further augmented inflammatory responses and apoptosis in the TNF-α-treated Caco-2 cells(P<0.05).Conversely,pterostilbene inhibited ER stress and restored autophagic flux in the IUGR colon and the TNF-α-treated cells(P<0.05).Pterostilbene also prevented the release of inflammatory cytokines and nuclear translocation of nuclear factor kappa B p65,reduced intestinal permeability and cell apoptosis,and facilitated the expression of intestinal tight junction proteins in the IUGR colon and the TNF-α-treated cells(P<0.05).Importantly,treatment with tunicamycin or autophagosome-lysosome binding inhibitor chloroquine blocked the positive effects of pterostilbene on inflammatory response,cell apoptosis,and intestinal barrier function in the TNF-α-exposed Caco-2 cells(P<0.05).Conclusion:Pterostilbene mitigates ER stress and promotes autophagic flux,thereby improving colon inflammation and barrier dysfunction in the IUGR piglets and the TNF-α-treated Caco-2 cells.展开更多
Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metaboli...Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon.However,the consequences of IUGR on bile acid metabolism in pigs remained unclear.The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of grow-ing pigs with IUGR using bile acid targeted metabolomics.Furthermore,we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight(NBW)pigs at different growth stages that were 7,21,and 28-day-old,and the average body weight(BW)of 25,50,and 100 kg of the NBW pigs.Results:The results showed that the plasma total bile acid concentration was higher(P<0.05)at the 25 kg BW stage and tended to increase(P=0.08)at 28-day-old in IUGR pigs.The hepatic gene expressions related to bile acid synthe-sis(CYP7A1,CYP27A1,and NTCP)were up-regulated(P<0.05),and the genes related to glucose and lipid metabolism(ATGL,HSL,and PC)were down-regulated(P<0.05)at the 25 kg BW stage in IUGR pigs when compared with the NBW group.Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs.The colonic concentrations of dehydrolithocholic acid and apocholic acid were increased(P<0.05),while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased(P<0.05)in IUGR pigs,when compared with the NBW pigs at the 25 kg BW stage.Moreover,Spearman’s correlation analysis revealed that colonic Unclassified_[Mogi-bacteriaceae],Lachnospira,and Slackia abundances were negatively correlated(P<0.05)with dehydrolithocholic acid,as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage.Conclusions:These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs,especially at the 25 kg BW stage,these effects being paralleled by a modification of bile acid derivatives concentra-tions in the colonic content.The plausible links between these modified parameters are discussed.展开更多
Background:Intrauterine growth restriction(IUGR)is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth(CUG)before weanling could significantly restore this negative influence.But ...Background:Intrauterine growth restriction(IUGR)is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth(CUG)before weanling could significantly restore this negative influence.But there was limited knowledge about the underlying mechanism of CUG occurrence.Methods:Eighty litters of newborn piglets were divided into normal birth weight(NBW)and IUGR groups according to birth weight.At 26 d,those piglets with IUGR but over average body weight of eighty litters of weaned piglets were considered as CUG,and the piglets with IUGR still below average body weight were considered as NCUG.This study was conducted to systemically compare the intestinal difference among NBW,CUG and NCUG weaned piglets considering the crucial role of the intestine for piglet growth.Results:The results indicated that the m RNA expression of nutrients(amino acids,glucose,and fatty acids)transporters,and mitochondrial electron transport chain(ETC)I were upregulated in CUG piglets'gut with improved morphology compared with those NCUG,as well as the ratio of P-AMPK/AMPK protein expression which is the indicator of energy metabolism.Meanwhile,CUG piglet's gut showed higher antioxidative capacity with increased SOD and GSHPx activity,decreased MDA levels,as well as higher m RNA expressions of Nrf2,Keap1,SOD,and GSH-Px.Furthermore,inflammatory parameters including TNF-α,IL-1β,IL-6,and IL-12 factors,and the activation of MAPK and NF-κB signaling pathways were significantly elevated in the NCUG intestine,while the protein expression of ZO-1,Occludin and Claudin-1 was reduced.The alpha diversity of fecal microbiota was higher in CUG piglets in contrast with NCUG piglets,and the increased beneficial bacteria and decreased pathogenic bacteria was also observed in CUG piglets.Conclusions:CUG piglet's intestine showed comprehensive restoration including higher nutrients transport,energy metabolism,antioxidant capacity,and intestinal physical barrier,while lower oxidative stress,inflammatory response,and pathogenic microbiota.展开更多
AIM: To investigate the intestine and body development of intrauterine growth retardation (IUGR) rats under early different protein diet and to analyze the correlation between leptin and intestine and body development...AIM: To investigate the intestine and body development of intrauterine growth retardation (IUGR) rats under early different protein diet and to analyze the correlation between leptin and intestine and body development.METHODS: An IUGR rat model was established by food restriction of pregnant female rats. Fifty-six neonatal IUGR rats and 24 neonatal normal rats were randomly divided into normal control group (C group), IUGR model group (SC group), low protein diet IUGR group (SL group), and high protein diet IUGR group (SH group). Eight rats were killed per group at wk 0, 4, and 12. Serum leptin, body weight (BW), body length (BL), intestinal weight (IW),intestinal length (IL), and intestinal disaccharidase (including lactase, maltase, and saccharase) were detected.RESULTS: BW (4.50±0.41 g), BL (5.96±0.40 cm), IW (0.05±0.01 g), and IL (15.9±2.8 cm) in neonatal IUGR rats were much lower than those in C group (6.01±0.55 g,6.26±0.44 cm, 0.10±0.02 g, 21.8±2.7 cm, P<0.05), while intestinal lactase and maltase activities were higher than those in C group. SH group showed the fastest catch up growth and their BW, BL, IW, and IL reached the C group level at wk 4. SC group showed relatively slower catch up growth than SH group, and their BW, BL, IW did not reach the C group level at wk 4. SL group did not show intestine and body catch up growth. Intestinal maltase [344±33 μmol/(min.g)] and saccharase activities [138±32μmol/(min.g)] in SL group were both markedly lower than those in C group [751±102, 258±27 μmol/(min.g), P<0.05].There were no significant differences in lactase activities at wk 4 and disaccharidase activities at wk 12 among all groups (P>0.05). The leptin level in SL group (0.58±0.12ng/mL) was the highest in all groups, and much lower in SH group (0.21±0.03 ng/mL) than that in any other IUGR groups at wk 4 (P<0.05). Leptin was negatively related to BW (r= -0.556, P = 0.001), IW (r= -0.692, P= 0.001)and IL (r = -0.738, P = 0.000) at wk 4, while no correlation was found at wk 12.CONCLUSION: High protein diet is a reasonable early nutritional mode to IUGR rats in promoting intestine and body catch up growth.展开更多
To investigate the effects of dietary supplementation with folic acid on growth performance, hepatic protein metabolism and serum biochemical indices of early-weaned intrauterine growth retardation (IUGR) piglets, 2...To investigate the effects of dietary supplementation with folic acid on growth performance, hepatic protein metabolism and serum biochemical indices of early-weaned intrauterine growth retardation (IUGR) piglets, 24 male (Durocx (LandracexYorkshire)) weaned (14-d-old) IUGR piglets were randomly divided into 3 treatments with 8 replicates of 1 piglet per replicate. The piglets in each treatment were fed basal diet supplementation with either 0 (control), 5 and 10 mg kg^-1 folic acid. The trial lasted for 21 d. Dietary folic acid supplementation reduced average daily feed intake (ADFI) (P〈0.05). In addition, the average daily gain (ADG) in 10 mg kg^-1 folic acid group was significantly decreased (P〈0.01) and the ratio of feed:gain (F/G) increased slightly (P〉0.05). Serum folic acid concentration increased (P〈0.01) with increasing folic acid inclusion, however, serum homocysteine concentration decreased significantly (P〈0.01). Enhanced serum urine nitrogen (SUN) and diminished serum total protein (TP) as well as liver TP content were observed in 10 mg kg^-1 folic acid group (/'〈0.05). Furthermore, the relative mRNA expressions of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (m-TOR) in liver were respectively tended to reduce (P=0.06) and significantly downregulated (P〈0.05) in 10 mg kg1 group, in compared with 5 mg kg1 group. However, when compared with control group, folic acid supplementation had no significant effect on the mRNA abundance of IGF- 1 and m-TOR. The results indicated that supplementation with 10 mg kg-I folic acid impaired growth performance and hepatic protein metabolism of early-weaned IUGR piglets while 5 mg kg-~ folic acid enriched diet exerted limited positive effects.展开更多
Objective To investigate the relationship between intrauterine growth retardation (IUGR) and endocrine parameters so as to assess the effects or the main endocrine ractors on IUGR. The concentrations of growth hormone...Objective To investigate the relationship between intrauterine growth retardation (IUGR) and endocrine parameters so as to assess the effects or the main endocrine ractors on IUGR. The concentrations of growth hormone(GH), insulin, T3, T4 and TSH were measured in umbilical cord blood, amniotic fluid and maternal serum.Methods The samples were collected from 23 pregnant women who were diagnosed as the full term IUGR, 42 normal full term pregnant women with normal infants’ weight were taken as control. Growth hormone and insulin were measured by radioimmunoassay. T3, T4 and TSH were investigated by micro-radioimmunoassay. Results The concentrations of growth hormone, insulin and T4 in umbilical cord blood were lower in IUGR than that in control group(GH4. 63μ/L vs 7. o1μg/L, insulin 1o. 68μIU/ml vs 31. 44μIU/ml, T487. 39nmol/L vs 138. 1onmol/L. P <o. o5, o. o5 and o. o5, respectively). The TSH concentration in umbilical cord blood was higher in IUGR than in control group (1o. 84μmIU/L vs 5. 75μmIU/L, P <o. o1 ). The concentration of growth hormone in maternal serum and the concentration of insulin in amniotic fluid were also lower in IUGR group than in control group(GH 1. 77μg/L vs 2. 74μg/L,P <o. o1, insulin 5. 84μIU/ml vs 15. 64μIU/ml, P <o. o1). Conclusion This study confirms that full term neonates with IUGR are abnormal in endocrine factors. The inadequacy of growth hormone may be one of the causes of IUGR. The relatlve scarcity of growth hormone and insulin seems to be a factor to compromise the fetus’ metabolism. Besides, the early hypothyrosis of infants with IUGR might protect them from unfavorable environment in the uterine.展开更多
To investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1),insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intra...To investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1),insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine growth retardation (IUGR) rats by giving the IUGR new born rats different protein level diet. Methods IUGR rat model was built by starvation of pregnant female rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4 groups: normal control group (C group); IUGR control group(S group), IUGR low-protein diet group (SL group), and IUGR high-protein diet group (SH group). Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT), and disaccharidase at the 4th week. Results (1) The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA were significantly higher than those of normal control group and IUGR control group. The intestinal weight and length, and the activities of lactase and saccharase of the SH group also reached the normal control group level. (2) The SL group kept on small size, the serum IGF1, IGFBP3, and most of intestinal histological indexes were all significantly lower than other groups. (3) IGF-1, IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight and length. Conclusions The serum IGF1 was a sensitive index to the catch-up growth. The early nutritional intervention of high-protein diet after birth is helpful for the catch-up growth of IUGR through promoting the intestinal development and the ab-sorption of展开更多
Background:Intestinal disorder is an important factor contributing to growth lag and high rates of morbidity and mortality of piglets with intrauterine growth retardation(IUGR).Resveratrol(RSV)and its derivative ptero...Background:Intestinal disorder is an important factor contributing to growth lag and high rates of morbidity and mortality of piglets with intrauterine growth retardation(IUGR).Resveratrol(RSV)and its derivative pterostilbene(PT)are natural stilbenes possessing various bioactivities,such as antioxidative and anti-inflammatory effects.This study compared the protective potential of RSV and PT on the intestinal redox status and gut microbiota in weanling piglets with IUGR.Methods:Eighteen male piglets of normal body weight(NBW)and 54 same-sex IUGR piglets were chosen according to their birth and weaning weights.The NBW piglets accepted a basal diet,while the IUGR piglets were allotted to one of three groups according to their body weight at weaning and received a basal diet,an RSV-supplemented diet(300 mg/kg),or a PT-supplemented diet(300 mg/kg),respectively.Results:Compared with IUGR piglets,both RSV and PT improved the IUGR-associated decrease in jejunal villus height and increases in plasma diamine oxidase activity and D-lactate level and jejunal apoptosis of piglets(P<0.05).Administering RSV and PT also enhanced jejunal superoxide dismutase activity and the mRNA and protein expression of superoxide dismutase 2 of IUGR piglets by promoting nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation(P<0.05).Comparatively,PT was more effective than RSV in elevating the villus height/crypt depth ratio and occludin mRNA and protein levels in the jejunum of IUGR piglets(P<0.05).PT was also superior to RSV in increasing Nrf2 nuclear translocation and inhibiting malondialdehyde accumulation in the jejunum of IUGR piglets(P<0.05).Additionally,RSV modulated the composition of cecal microbiota of IUGR piglets,as evidenced by increasing the prevalence of the phylum Bacteroidetes and the genera Prevotella,Faecalibacterium,and Parabacteroides and inhibiting the growth of the phylum Proteobacteria and its genera Escherichia and Actinobacillus(P<0.05).Moreover,RSV significantly increased the butyrate concentration in the cecum of IUGR piglets(P<0.05).Conclusion:PT is more potent than RSV to prevent intestinal oxidative stress,while RSV has a stronger capacity to regulate gut microbiota compared to PT.展开更多
Intrauterine growth retardation (IU- GR) causes significantly negative effects on the meth- ylation status of genes related to cell apoptosis com- pared with normal body weight (NBW) piglets. Thus, the objective o...Intrauterine growth retardation (IU- GR) causes significantly negative effects on the meth- ylation status of genes related to cell apoptosis com- pared with normal body weight (NBW) piglets. Thus, the objective of the present study was to exam- ine the effects of maternal dietary folic acid supple- mentation on genes expression profile for hepatic ap- optosis in IUGR and NBW piglets. Twenty four York- shire gilts were allocated randomly to one of the two diets : control ( C, folic acid 1.3 mg/kg) or folic acid supplementation ( FS, folic acid 30 mg/kg) after mat- ing. Gene expressions in liver samples were deter- mined and revealed that the mRNA expressions of p53 ,BCL-2 associated X protein (Bax), and Cyclin- dependent kinase inhibitor 1A (CDKN1A) were up-regulated in IUGR piglets compared with NBW pig- lets fed C diets,but could be reversed by maternal fo- lic acid supplementation. The expressions of vascular endothelial growth factor (VEGF), Serine-protein Ki- nase-Ataxia Telangiectasia Mutated (ATM) ,and Cad- herin-associated protein-beta-catenin 1 ( CTNNB1 ) were influenced by maternal folic acid supplementa- tion significantly, but were not influenced by birth weight. Expression of p53 binding protein-MDM-2 ( MDM-2 ) remained unchanged. In conclusion, these results demonstrated that maternal folic acid supple- mentation could exert positive effects on genes related to apoptosis in IUGR and NBW piglets, which might facilitate their postnatal health and growth perform- alice.展开更多
基金the Key Project of Regional Innovation and Development Joint Fund of the National Natural Science Foundation of China(U20A2056)the Special Funds for Construction of Innovative Provinces in Hunan Province(2019RS3022).
文摘Background Intrauterine growth retardation(IUGR)is one of the major constraints in animal production.Our previ-ous study showed that piglets with IUGR are associated with abnormal bile acid(BA)metabolism.This study explored whether dietary BA supplementation could improve growth performance and colonic development,function,micro-biota,and metabolites in the normal birth weight(NBW)and IUGR piglets.A total of 48 weaned piglets(24 IUGR and 24 NBW)were allocated to four groups(12 piglets per group):(i)NBW group,(ii)NBW+BA group,(iii)IUGR group,and(iv)IUGR+BA group.Samples were collected after 28 days of feeding.Results The results showed that dietary BA supplementation increased the length and weight of the colon and colon weight to body weight ratio,while decreased the plasma diamine oxidase(DAO)concentration in the NBW pig-lets(P<0.05).Dietary BA supplementation to IUGR piglets decreased(P<0.05)the plasma concentrations of D-lactate and endotoxin and colonic DAO and endotoxin,suggesting a beneficial effect on epithelial integrity.Moreover,dietary BA supplementation to NBW and IUGR piglets increased Firmicutes abundance and decreased Bacteroidetes abundance(P<0.05),whereas Lactobacillus was the dominant genus in the colon.Metabolome analysis revealed 65 and 51 differential metabolites in the colon of piglets fed a diet with/without BA,respectively,which was associated with the colonic function of IUGR piglets.Furthermore,dietary BA supplementation to IUGR piglets upregulated the expressions of CAT,GPX,SOD,Nrf1,IL-2,and IFN-γin colonic mucosa(P<0.05).Conclusions Collectively,dietary BA supplementation could improve the colonic function of IUGR piglets,which was associated with increasing proportions of potentially beneficial bacteria and metabolites.Furthermore,BA shows a promising application prospect in improving the intestinal ecosystem and health of animals.
基金supported by grants from the National Natural Science Foundation of China (Nos.31902197 and 31802094)the Natural Science Foundation of Jiangsu Province (No.BK20180531)。
文摘Background:Endoplasmic reticulum(ER)stress and autophagy are implicated in the pathophysiology of intestinal inflammation;however,their roles in intrauterine growth retardation(IUGR)-induced colon inflammation are unclear.This study explored the protective effects of natural stilbene pterostilbene on colon inflammation using the IUGR piglets and the tumor necrosis factor alpha(TNF-α)-treated human colonic epithelial cells(Caco-2)by targeting ER stress and autophagy.Results:Both the IUGR colon and the TNF-α-treated Caco-2 cells exhibited inflammatory responses,ER stress,and impaired autophagic flux(P<0.05).The ER stress inducer tunicamycin and the autophagy inhibitor 3-methyladenine further augmented inflammatory responses and apoptosis in the TNF-α-treated Caco-2 cells(P<0.05).Conversely,pterostilbene inhibited ER stress and restored autophagic flux in the IUGR colon and the TNF-α-treated cells(P<0.05).Pterostilbene also prevented the release of inflammatory cytokines and nuclear translocation of nuclear factor kappa B p65,reduced intestinal permeability and cell apoptosis,and facilitated the expression of intestinal tight junction proteins in the IUGR colon and the TNF-α-treated cells(P<0.05).Importantly,treatment with tunicamycin or autophagosome-lysosome binding inhibitor chloroquine blocked the positive effects of pterostilbene on inflammatory response,cell apoptosis,and intestinal barrier function in the TNF-α-exposed Caco-2 cells(P<0.05).Conclusion:Pterostilbene mitigates ER stress and promotes autophagic flux,thereby improving colon inflammation and barrier dysfunction in the IUGR piglets and the TNF-α-treated Caco-2 cells.
基金supported by the National Natural Science Foundation of China(U20A2056)Special Funds for Construction of Innovative Provinces in Hunan Province(2019RS3022).
文摘Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon.However,the consequences of IUGR on bile acid metabolism in pigs remained unclear.The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of grow-ing pigs with IUGR using bile acid targeted metabolomics.Furthermore,we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight(NBW)pigs at different growth stages that were 7,21,and 28-day-old,and the average body weight(BW)of 25,50,and 100 kg of the NBW pigs.Results:The results showed that the plasma total bile acid concentration was higher(P<0.05)at the 25 kg BW stage and tended to increase(P=0.08)at 28-day-old in IUGR pigs.The hepatic gene expressions related to bile acid synthe-sis(CYP7A1,CYP27A1,and NTCP)were up-regulated(P<0.05),and the genes related to glucose and lipid metabolism(ATGL,HSL,and PC)were down-regulated(P<0.05)at the 25 kg BW stage in IUGR pigs when compared with the NBW group.Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs.The colonic concentrations of dehydrolithocholic acid and apocholic acid were increased(P<0.05),while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased(P<0.05)in IUGR pigs,when compared with the NBW pigs at the 25 kg BW stage.Moreover,Spearman’s correlation analysis revealed that colonic Unclassified_[Mogi-bacteriaceae],Lachnospira,and Slackia abundances were negatively correlated(P<0.05)with dehydrolithocholic acid,as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage.Conclusions:These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs,especially at the 25 kg BW stage,these effects being paralleled by a modification of bile acid derivatives concentra-tions in the colonic content.The plausible links between these modified parameters are discussed.
基金the Natural Science Foundation of Guangdong Province(2021A1515010944)the National Natural Science Foundation of China(31402082 and 32272894)。
文摘Background:Intrauterine growth restriction(IUGR)is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth(CUG)before weanling could significantly restore this negative influence.But there was limited knowledge about the underlying mechanism of CUG occurrence.Methods:Eighty litters of newborn piglets were divided into normal birth weight(NBW)and IUGR groups according to birth weight.At 26 d,those piglets with IUGR but over average body weight of eighty litters of weaned piglets were considered as CUG,and the piglets with IUGR still below average body weight were considered as NCUG.This study was conducted to systemically compare the intestinal difference among NBW,CUG and NCUG weaned piglets considering the crucial role of the intestine for piglet growth.Results:The results indicated that the m RNA expression of nutrients(amino acids,glucose,and fatty acids)transporters,and mitochondrial electron transport chain(ETC)I were upregulated in CUG piglets'gut with improved morphology compared with those NCUG,as well as the ratio of P-AMPK/AMPK protein expression which is the indicator of energy metabolism.Meanwhile,CUG piglet's gut showed higher antioxidative capacity with increased SOD and GSHPx activity,decreased MDA levels,as well as higher m RNA expressions of Nrf2,Keap1,SOD,and GSH-Px.Furthermore,inflammatory parameters including TNF-α,IL-1β,IL-6,and IL-12 factors,and the activation of MAPK and NF-κB signaling pathways were significantly elevated in the NCUG intestine,while the protein expression of ZO-1,Occludin and Claudin-1 was reduced.The alpha diversity of fecal microbiota was higher in CUG piglets in contrast with NCUG piglets,and the increased beneficial bacteria and decreased pathogenic bacteria was also observed in CUG piglets.Conclusions:CUG piglet's intestine showed comprehensive restoration including higher nutrients transport,energy metabolism,antioxidant capacity,and intestinal physical barrier,while lower oxidative stress,inflammatory response,and pathogenic microbiota.
基金Supported Dy the Science and Technology Bureau Foundation of Guangdong Province, No. 99M04815G
文摘AIM: To investigate the intestine and body development of intrauterine growth retardation (IUGR) rats under early different protein diet and to analyze the correlation between leptin and intestine and body development.METHODS: An IUGR rat model was established by food restriction of pregnant female rats. Fifty-six neonatal IUGR rats and 24 neonatal normal rats were randomly divided into normal control group (C group), IUGR model group (SC group), low protein diet IUGR group (SL group), and high protein diet IUGR group (SH group). Eight rats were killed per group at wk 0, 4, and 12. Serum leptin, body weight (BW), body length (BL), intestinal weight (IW),intestinal length (IL), and intestinal disaccharidase (including lactase, maltase, and saccharase) were detected.RESULTS: BW (4.50±0.41 g), BL (5.96±0.40 cm), IW (0.05±0.01 g), and IL (15.9±2.8 cm) in neonatal IUGR rats were much lower than those in C group (6.01±0.55 g,6.26±0.44 cm, 0.10±0.02 g, 21.8±2.7 cm, P<0.05), while intestinal lactase and maltase activities were higher than those in C group. SH group showed the fastest catch up growth and their BW, BL, IW, and IL reached the C group level at wk 4. SC group showed relatively slower catch up growth than SH group, and their BW, BL, IW did not reach the C group level at wk 4. SL group did not show intestine and body catch up growth. Intestinal maltase [344±33 μmol/(min.g)] and saccharase activities [138±32μmol/(min.g)] in SL group were both markedly lower than those in C group [751±102, 258±27 μmol/(min.g), P<0.05].There were no significant differences in lactase activities at wk 4 and disaccharidase activities at wk 12 among all groups (P>0.05). The leptin level in SL group (0.58±0.12ng/mL) was the highest in all groups, and much lower in SH group (0.21±0.03 ng/mL) than that in any other IUGR groups at wk 4 (P<0.05). Leptin was negatively related to BW (r= -0.556, P = 0.001), IW (r= -0.692, P= 0.001)and IL (r = -0.738, P = 0.000) at wk 4, while no correlation was found at wk 12.CONCLUSION: High protein diet is a reasonable early nutritional mode to IUGR rats in promoting intestine and body catch up growth.
基金supported by the earmarked fund for China Agriculture Research System (CARS-36)the Program for Changjiang Scholars and Innovative Research Team in University,Ministry of Education of China (IRT0555)
文摘To investigate the effects of dietary supplementation with folic acid on growth performance, hepatic protein metabolism and serum biochemical indices of early-weaned intrauterine growth retardation (IUGR) piglets, 24 male (Durocx (LandracexYorkshire)) weaned (14-d-old) IUGR piglets were randomly divided into 3 treatments with 8 replicates of 1 piglet per replicate. The piglets in each treatment were fed basal diet supplementation with either 0 (control), 5 and 10 mg kg^-1 folic acid. The trial lasted for 21 d. Dietary folic acid supplementation reduced average daily feed intake (ADFI) (P〈0.05). In addition, the average daily gain (ADG) in 10 mg kg^-1 folic acid group was significantly decreased (P〈0.01) and the ratio of feed:gain (F/G) increased slightly (P〉0.05). Serum folic acid concentration increased (P〈0.01) with increasing folic acid inclusion, however, serum homocysteine concentration decreased significantly (P〈0.01). Enhanced serum urine nitrogen (SUN) and diminished serum total protein (TP) as well as liver TP content were observed in 10 mg kg^-1 folic acid group (/'〈0.05). Furthermore, the relative mRNA expressions of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (m-TOR) in liver were respectively tended to reduce (P=0.06) and significantly downregulated (P〈0.05) in 10 mg kg1 group, in compared with 5 mg kg1 group. However, when compared with control group, folic acid supplementation had no significant effect on the mRNA abundance of IGF- 1 and m-TOR. The results indicated that supplementation with 10 mg kg-I folic acid impaired growth performance and hepatic protein metabolism of early-weaned IUGR piglets while 5 mg kg-~ folic acid enriched diet exerted limited positive effects.
文摘Objective To investigate the relationship between intrauterine growth retardation (IUGR) and endocrine parameters so as to assess the effects or the main endocrine ractors on IUGR. The concentrations of growth hormone(GH), insulin, T3, T4 and TSH were measured in umbilical cord blood, amniotic fluid and maternal serum.Methods The samples were collected from 23 pregnant women who were diagnosed as the full term IUGR, 42 normal full term pregnant women with normal infants’ weight were taken as control. Growth hormone and insulin were measured by radioimmunoassay. T3, T4 and TSH were investigated by micro-radioimmunoassay. Results The concentrations of growth hormone, insulin and T4 in umbilical cord blood were lower in IUGR than that in control group(GH4. 63μ/L vs 7. o1μg/L, insulin 1o. 68μIU/ml vs 31. 44μIU/ml, T487. 39nmol/L vs 138. 1onmol/L. P <o. o5, o. o5 and o. o5, respectively). The TSH concentration in umbilical cord blood was higher in IUGR than in control group (1o. 84μmIU/L vs 5. 75μmIU/L, P <o. o1 ). The concentration of growth hormone in maternal serum and the concentration of insulin in amniotic fluid were also lower in IUGR group than in control group(GH 1. 77μg/L vs 2. 74μg/L,P <o. o1, insulin 5. 84μIU/ml vs 15. 64μIU/ml, P <o. o1). Conclusion This study confirms that full term neonates with IUGR are abnormal in endocrine factors. The inadequacy of growth hormone may be one of the causes of IUGR. The relatlve scarcity of growth hormone and insulin seems to be a factor to compromise the fetus’ metabolism. Besides, the early hypothyrosis of infants with IUGR might protect them from unfavorable environment in the uterine.
文摘To investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1),insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine growth retardation (IUGR) rats by giving the IUGR new born rats different protein level diet. Methods IUGR rat model was built by starvation of pregnant female rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4 groups: normal control group (C group); IUGR control group(S group), IUGR low-protein diet group (SL group), and IUGR high-protein diet group (SH group). Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT), and disaccharidase at the 4th week. Results (1) The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA were significantly higher than those of normal control group and IUGR control group. The intestinal weight and length, and the activities of lactase and saccharase of the SH group also reached the normal control group level. (2) The SL group kept on small size, the serum IGF1, IGFBP3, and most of intestinal histological indexes were all significantly lower than other groups. (3) IGF-1, IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight and length. Conclusions The serum IGF1 was a sensitive index to the catch-up growth. The early nutritional intervention of high-protein diet after birth is helpful for the catch-up growth of IUGR through promoting the intestinal development and the ab-sorption of
基金supported by the National Natural Science Foundation of China(Nos.31802094,31772634)the Natural Science Foundation of Jiangsu Province(No.BK20180531)+1 种基金the Postdoctoral Research Foundation of China(Nos.2018 M632320,2019 T120436)the Open Project of Shanghai Key Laboratory of Veterinary Biotechnology(No.klab201710).
文摘Background:Intestinal disorder is an important factor contributing to growth lag and high rates of morbidity and mortality of piglets with intrauterine growth retardation(IUGR).Resveratrol(RSV)and its derivative pterostilbene(PT)are natural stilbenes possessing various bioactivities,such as antioxidative and anti-inflammatory effects.This study compared the protective potential of RSV and PT on the intestinal redox status and gut microbiota in weanling piglets with IUGR.Methods:Eighteen male piglets of normal body weight(NBW)and 54 same-sex IUGR piglets were chosen according to their birth and weaning weights.The NBW piglets accepted a basal diet,while the IUGR piglets were allotted to one of three groups according to their body weight at weaning and received a basal diet,an RSV-supplemented diet(300 mg/kg),or a PT-supplemented diet(300 mg/kg),respectively.Results:Compared with IUGR piglets,both RSV and PT improved the IUGR-associated decrease in jejunal villus height and increases in plasma diamine oxidase activity and D-lactate level and jejunal apoptosis of piglets(P<0.05).Administering RSV and PT also enhanced jejunal superoxide dismutase activity and the mRNA and protein expression of superoxide dismutase 2 of IUGR piglets by promoting nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation(P<0.05).Comparatively,PT was more effective than RSV in elevating the villus height/crypt depth ratio and occludin mRNA and protein levels in the jejunum of IUGR piglets(P<0.05).PT was also superior to RSV in increasing Nrf2 nuclear translocation and inhibiting malondialdehyde accumulation in the jejunum of IUGR piglets(P<0.05).Additionally,RSV modulated the composition of cecal microbiota of IUGR piglets,as evidenced by increasing the prevalence of the phylum Bacteroidetes and the genera Prevotella,Faecalibacterium,and Parabacteroides and inhibiting the growth of the phylum Proteobacteria and its genera Escherichia and Actinobacillus(P<0.05).Moreover,RSV significantly increased the butyrate concentration in the cecum of IUGR piglets(P<0.05).Conclusion:PT is more potent than RSV to prevent intestinal oxidative stress,while RSV has a stronger capacity to regulate gut microbiota compared to PT.
基金supported by Program of Changjiang Scholars and Innovative Research Team in University of China(IRT0555-5)
文摘Intrauterine growth retardation (IU- GR) causes significantly negative effects on the meth- ylation status of genes related to cell apoptosis com- pared with normal body weight (NBW) piglets. Thus, the objective of the present study was to exam- ine the effects of maternal dietary folic acid supple- mentation on genes expression profile for hepatic ap- optosis in IUGR and NBW piglets. Twenty four York- shire gilts were allocated randomly to one of the two diets : control ( C, folic acid 1.3 mg/kg) or folic acid supplementation ( FS, folic acid 30 mg/kg) after mat- ing. Gene expressions in liver samples were deter- mined and revealed that the mRNA expressions of p53 ,BCL-2 associated X protein (Bax), and Cyclin- dependent kinase inhibitor 1A (CDKN1A) were up-regulated in IUGR piglets compared with NBW pig- lets fed C diets,but could be reversed by maternal fo- lic acid supplementation. The expressions of vascular endothelial growth factor (VEGF), Serine-protein Ki- nase-Ataxia Telangiectasia Mutated (ATM) ,and Cad- herin-associated protein-beta-catenin 1 ( CTNNB1 ) were influenced by maternal folic acid supplementa- tion significantly, but were not influenced by birth weight. Expression of p53 binding protein-MDM-2 ( MDM-2 ) remained unchanged. In conclusion, these results demonstrated that maternal folic acid supple- mentation could exert positive effects on genes related to apoptosis in IUGR and NBW piglets, which might facilitate their postnatal health and growth perform- alice.