Effect Of Tributyrin On Liver Function And Lipid Metabolism Of Piglets With Intrauterine Growth Retardation

Intrauterine growth retardation(IUGR)generally refers to the fetus are influenced by various factors in uterine,resulting in low birth weight.At present,there is a high incidence of IUGR in human and animal production.Numerous studies have indicated that IUGR may have multiple adverse effects on the normal metabolism of the body after birth.IUGR can cause high mortality rates,slow growth,and long-term negative effects on the growth and development of piglets.Therefore,it is important for researchers to find nutritional regulation and methods for the early development of IUGR neonates and animal production.Tributyrin(TB)is a kind prodrug of butyrate,with the basic characteristics of butyrate.Tributyrin has been widely reported to be effective in promoting the growth and attenuating the damage of animals,which can improve the absorption and utilization of nutrients by body.Therefore,the present experiment was designed to evaluate the effect of TB on liver function and metabolism of liver in piglets with IUGR,for providing a theoretical basis to the application of scientific research.1.Effect of tributyrin on biochemical indexes of blood and liver growth of piglets with intrauterine growth retardationThe present experiment selected 8 normal birth weight(NBW)and 16 IUGR newborn piglets.The NBW piglets were assigned to the NBW group,2 IUGR piglets from 1 litter were randomly assigned to the IUGR and IT(tributyrin supplementation)groups(n=8/group,4 males and 4 females).All piglets were weaned on 7th day and fed with warm milk substitute diets per meal every 3 h by using a bottle.The piglets of NBW and IUGR groups fed with a basic milk diet,and piglets of IT group fed with a basic milk diet supplemented with 0.10%TB to 21st day.At 21 days of age,6 piglets(3 males and females)with nearly equal body weights(within groups)were selected from each group(n = 8/group)and were weighed prior to euthanization.All piglets were killed by administering an intramuscular injection of sodium pentobarbital(50 mg/kg of body weight)at 2 h after the last meal.Serum physiological and biochemical indexes,liver weight,IGF-1 content,mRNA expression levels of IGF-1 and Ghrelin in the liver of piglets were determined.The results showed that:(1)compared with the NBW group,the urea and total bilirubin levels of serum were significantly decreased(P<0.05),the total protein and creatinine levels of serum were significantly increased(P<0.05)in piglets with IUGR.The content of total protein,albumin and creatinine in serum were significantly lower(P<0.05)in IT group compared with IUGR group.The content of urea and total bilirubin in IT group was significantly higher(P<0.05)than that of IUGR group.(2)The weight of the liver in piglets with IUGR was significantly lower(P<0.05)than that of the NBW and IT groups.There was no significant differences(P>0.05)of the liver index between the IUGR and NBW groups,but the liver index in the IT group was significantly higher(P<0.05)than that in the NBW and IUGR groups.The content of IGF-1 in the liver of the IUGR group was significantly lower(P<0.05)than that in the NBW and IT groups.(3)The IGF-1mRNA expression in the liver of IUGR group was significantly lower(P<0.05)than that in the NBW and IT groups,and the IGF-1 mRNA expression of IT group was slightly lower(P>0.05)than that in the NBW group.The Ghrelin mRNA expression in the liver of IUGR group was significantly higher than that in NBW and IT groups(P<0.05),and that in the IT group had a slightly increase(P>0.05)as compared to NBW group.In conclusion,dietary supplementation with tributyrin had a significant promoting effect on the growth of the liver in IUGR piglets,and the effect of tributyrin may be related to the regulation of IGF-1.2.Effect of tributyrin on the immunity function and antioxidative enzymes activity of the liver in piglets with intrauterine growth retardationThe experiment was designed same with the experiment 1.The histological observation,contents of TNF-a and IL4,and TNF-?,IL?,IL4,and IL10 mRNA expression in the liver were measured.The activities of antioxidative enzyme in the liver and the function of mitochondria in the liver were determined.The results showed that:(1)the damage of central veins and portal congestion were observed in the liver of piglets with IUGR,and which were not observed in NBW and IT groups.(2)The contents of TNF-a and IL4 in the liver of IUGR group were significantly higher(P<0.05)than those of NBW and IT groups.(3)Compared with NBW group,IUGR significantly increased(P<0.01)the IL1? and IL4 mRNA expressions and significantly decreased(P<0.05)the IL10 mRNA expression in the liver.The IL1? mRNA expression of IT group was significantly lower(P<0.01)than that of NBW group,but the IL4 mRNA expression of IT group was significantly higher(P<0.01)than that of IUGR and NBW groups.The IL10 mRNA expression of IT group was significantly lower(P<0.05)than that of NBW group,but higher than that of IUGR group(P>0.05).(4)Compared with the NBW group,the activity of GSH-Px in the liver of IUGR group was significantly decreased(P<0.05),and the content of MDA in the liver of IUGR group was significantly increased(P<0.01).Compared with IUGR group,the activities of GSH-Px and SOD,and content of GSH in IT group were significantly increased(P<0.05),and the content of MDA in IT group was significantly decreased(P<0.01).Compared with NBW group,the content of GSH and activity of T-AOC in the liver of IT group were significantly increased(P<0.05),and the content of MDA was significantly decreased(P<0.01)in the liver of IT group.(5)Compared with NBW group,the activities of SDH and Mn-SOD in the mitochondria of liver of IUGR group were significantly decreased(P<0.05).The activities of SDH and Mn-SOD in the mitochondria of liver of IT group were significantly increased(P<0.05)than those in IUGR group,and there was no significant differences(P>0.05)between IT and NBW groups.In conclusion,the present study indicated that tributyrin was helpful in improving the antioxidant capacities of liver and mitochondrial of liver for IUGR piglet.These help of tributyrin might be affected on molecule level.3.Effect of tributyrin on insulin resistance and lipid metabolism in piglets with intrauterine growth retardationThe experiment was designed same with the experiment 1.Insulin and leptin levels in the serum,contents of TC and TG in the serum and liver,contents of HDL-C and LDL-C in the serum,concentration of glycogen,NEFA,and activities of LPL and HL in the liver were measured.Liver INSR,IRS1 and PIK3C3,Akt2,SREBP-1 and LXRa and PPARa,FAS and ACC?,SCD,FABP mRNA expression were also determined.The results showed that:(1)compared with NBW group,insulin level of serum and HOMA-IR values were significantly increased(P<0.05)in IUGR group,while the HOMA-IR value of IT group was significantly decreased(P<0.05).The insulin level in the serum and HOMA-IR value of IT group were significantly lower(P<0.05)than that of IUGR group.(2)Compared with NBW group,the contents of TC,TG and NEFA in the liver of IUGR group were significantly increased(P<0.05).Compared with IUGR group,contents of TG in the serum and glycogen in the liver of IT group were significantly increased(P<0.05),levels of LDL-C,HDL-C in the serum and concentrations of TG,NEFA in the liver were significantly decreased(P<0.05)in IT group.Compared with NBW group,contents of TC and NEFA in the liver of IT group was still higher(P<0.05),but the other parameters were not significantly different with IT group(P>0.05).(3)Compared with NBW group,activities of HL,LPL(P<0.05)and TL(P<0.01)in the liver of IUGR group were significantly decreased.The activity of TL in the liver of IT group was still lower(P<0.05)than that of NBW group.There were no significant differences of HL and LPL activities between NBW and IT groups(P>0.05).The activities of HL,LPL and TL in the liver of IT group was significantly higher than that in IUGR group(P<0.05).(4)Compared with NBW group,INSR,SREBP-1,LXRa,PPARa,FAS and ACCp mRNA expression of IUGR group were significantly up-regulated(P<0.05),SCD mRNA expression of IUGR group was significantly down-regulated(P<0.05),FAS mRNA expression was significantly up-regulated(P<0.05)and Akt2 mRNA expression was significantly down-regulated(P<0.05)in IT group.Compared with IUGR group,SCD mRNA expression was significantly increased in IT group(P<0.05),INSR,Akt2,SREBP-1,LXRa,PPARa,and ACC? mRNA expression were significantly down-regulated(P<0.05)in IT group.There were no significant differences(P>0.05)of other parameters within groups.In conclusion,dietary supplementation with tributyrin was helpful in alleviating the abnormal metabolism of IUGR piglets through increasing the activities of lipid transport enzymes and their related genes mRNA expression.In conclusion,piglets with intrauterine growth retardation showed abnormal metabolism.Especially the liver growth of piglets with IUGR was inhibited and its normal function was seriously affected,which were related with gene mRNA expression.Dietary supplementation with 0.10%tributyrin could effectively improve liver growth and attenuate these disorder metabolism situation of IUGR piglets through gene mRNA expression regulation.