Effects Of Dietary Addition Of Curcumin And Resveratrol On Antioxidant And Lipid Metabolism In Liver Of Weaned Piglets

In the modern intensive pig production model,in order to improve the efficiency of farming,early weaning techniques are often used.Early weaning of piglets is often caused by immature autoimmune and digestive systems,as well as environmental stimuli,which often induce immune stress,resulting in "early weaning syndrome in piglets".Weaning stress usually affects the body’s lipid metabolism,organ development and production performance in weaned piglets.As the largest immune organ and metabolic organ of the body,the liver plays an important role in regulating fat and energy metabolism under stress conditions.Usually people add antibiotics to the diet or drinking water of weaned pigs to improve the immunity of weaned pigs.However,the use of antibiotics has many drawbacks.The development and use of"Antibiotic substitute or No antibiotics" products is the trend of modern animal husbandry development.Curcumin and resveratrol are natural plant extracts that are non-toxic and have a wide range of nutritional and pharmacological functions,but are less bioavailable.The aim of this study was to investigate the effects of dietary supplementation with curcumin,resveratrol and their combination on growth performance,liver antioxidant capacity,m6A methylation modification,lipid metabolism and mitochondrial function in weaned piglets,and to determine curcumin and resveratrol,Whether the combined use can play a synergistic role to improve its biological characteristics,provide a scientific basis for piglet production and nutritional regulation,and provide a new idea for the development of alternative antibiotic products.In the first experiment,the effects of adding curcumin and resveratrol on the growth performance,digestibility and blood parameters of weaned piglets.A total of 180 28-day-old weaned Duchangda ternary crossbred piglets were randomly divided into 6 groups according to the principle of similar body weight,with 3 replicates in each group and 10 replicates in each group.The CON group was fed the basal diet,and the ANT,CUR,RES,LRC,and HRC groups were supplemented with 300 mg/kg compound antibiotic,300 mg/kg curcumin,and 300 mg/kg resveratrol in the basal diet.The diet of 100 mg/kg curcumin and resveratrol,300 mg/kg curcumin and resveratrol was tested for 28 days.The results showed that(1)compared with the CON group,the ANT group and the HRC group significantly increased the average daily weight gain ADG of weaned piglets(P<0.05);the HRC group significantly increased the average daily feed intake of the weaned piglets ADIF(P<0.05);ANT group can significantly reduce the weight-to-weight ratio of weaned piglets F/G(P<0.05),and other additive groups can reduce the F/G of weaned piglets,but the difference is not significant(P>0.05).(2)Compared with CON group,the apparent digestibility of crude protein in ANT group was significantly increased(P<0.05);the apparent digestibility of crude fat in weaned piglets in ANT,HRC and RES groups was significantly increased(P<0.05);Compared with the CON group,there was no significant difference in the apparent digestibility of crude fiber,crude ash and dry matter in the weaned pigs(P>0.05).(3)Compared with the CON group,the serum triglyceride(TG)levels in the HRC group and the RES group decreased significantly(P<0.05),and the serum triglyceride levels in the other additive groups were not significantly different(P>0.05);The levels of serum TC and LDL-C in each additive group decreased,but the difference was not significant(P>0.05).(4)Compared with CON group,serum AST content in HRC group was significantly lower(P<0.05).Compared with the CON group and the ANT group,the levels of ALT in the HRC group and the RES group were significantly lower(P<0.05),and the serum ALT levels in the LRC group and the CUR group were significantly decreased(P<0.10).(5)Compared with the CON group,the serum GSH-PX activity of each additive group was not significantly different(P>0.05);the serum T-AOC activity of the HRC group,RES group and CUR group was significantly increased(P<0.05);Compared with the HRC group,the serum CAT activity was significantly increased(P<0.05),and the RES group showed a significant increase(P=0.064).Compared with CON group,ANT group,HRC group,RES group and CUR group could significantly reduce serum MDA content in weaned piglets(P<0.05).In the second experiment,the effects of dietary resveratrol and resveratrol on the liver antioxidant capacity and liver methylation of m6A RNA in weaned piglets were studied.The experimental design scheme is the same as experiment 1.The results showed that(1)compared with the CON group,each additive group can raise liver catalase(CAT),glutathione peroxidase GPX and glutathione reductase GR in weaned piglets at different levels.The activity,but the difference was not significant(P>0.05);HRC,RES,CUR group significantly increased the activity of total superoxide dismutase T-SOD in the liver of weaned piglets(P<0.05);total antioxidant in HRC and RES groups T-AOC levels were significantly elevated(P<0.05).(2)Compared with the group of CON,the contents of MDA in the liver of weaned piglets in HRC,RES and CUR groups were significantly lower(P<0.05).(3)Compared with CON,ANT,HRC,LRC,RES,and CUR groups can increase liver glutathione GSH in weaned piglets and reduce oxidized glutathione GSSG in weaned piglets at a certain level,but the difference is not significant.(P>0.05);the difference of GSH/GSSG levels in weaned piglets was not significant(P>0.05).(4)Compared with the CON group,the HRC group significantly up-regulated the liver CAT gene expression level in weaned piglets(P<0.05),and the liver CAT gene expression level in the HRC group was significantly higher than that in the other additive groups(P<0.05);In contrast,the HRC group significantly up-regulated the expression of SOD2 gene in the liver of weaned piglets(P<0.05).Compared with the CON group,the expression levels of NRF2,GPX,GCLM and GCLC in the liver of the weaned piglets were up-regulated,but the difference was not Significant(P>0.05);the gene expression level of liver HO-1 in HRC group was significantly up-regulated(P<0.05).(5)Compared with the CON group,the HRC group significantly up-regulated the expression of METTL3 gene in the liver of weaned piglets(P<0.05);the HRC,RES,and CUR groups significantly up-regulated the expression of YTHPF2 gene(P<0.05),and the liver between each additive group the expression of FTO gene was not significantly different(P>0.05).Compared with CON group,HRC and CUR groups significantly up-regulated the expression of ALKBH5 gene in liver(P<0.05).In experiment 3,the effects of curcumin and resveratrol on liver lipid metabolism and mitochondrial function in weaned piglets were studied.The experimental design scheme is the same as experiment 1.The results showed that(1)compared with CON group,HRC group can significantly reduce liver TC content in weaned piglets(P<0.05);liver TG content in HRC,RES,CUR group was significantly lower(P<0.05);HRC and CUR groups significantly increased the activity of lipoprotein lipase LPL in weaned piglets(P<0.05),and the activity of lipoprotein lipase LPL in HRC group was significantly higher than that in LRC group(P<0.05).(2)Compared with CON group,the expressions of PPAR-y,FAS and ACCa mRNA in ANT,HRC,LRC,RES and CUR groups were not significantly different(P>0.05),but compared with ANT group,ACCa gene in HRC group The expression of ACCβ mRNA was significantly decreased in the HRC,RES and CUR groups compared with the CON group(P<0.05).Compared with the CON group and the ANT group,the SCD gene in the HRC and RES groups was significantly lower than that in the CON group.The expression of mRNA was significantly decreased(P<0.05),and the expression of SCD mRNA in HRC group was significantly lower than that in LRC and CUR groups(P<0.05).The expression levels of SREBP-1 mRNA in the HRC,LRC,RES,and CUR groups were significantly lower than those in the CON group and the ANT group(P<0.05).Compared with CON,ANT and LRC groups,the expression of PPAR-α mRNA in HRC group was significantly increased(P<0.05),and the expression of PPAR-α gene in RES and CUR groups was significantly increased(P<0.10).Compared with CON,the expression of CPT1,PPAR-y and SIRT1 mRNA in each additive group was improved,but the difference was not significant(P>0.05).Compared with CON,ANT and LRC groups,the expression of PGC1 gene in HRC group was significantly increased(P<0.05).Compared with CON group,the expression of PGC1 gene in RES and CUR groups increased significantly(P = 0.069),(P=0.081).Compared with the CON group,the expression of NRF1 gene in the liver of weaned piglets was significantly up-regulated in the HRC group(P<0.05),and the expression of NRF1 gene in the liver of ANT,RES and CUR groups was also significantly up-regulated(P=0.083),(P=0.051).),(P=0.065).Compared with the CON group,the HRC group significantly up-regulated the expression of TFAM gene in the liver of weaned piglets(P<0.05),and the expression of TFAM gene in the liver of RES group increased(P=0.061).(3)Compared with the CON group,the content of ATP in the liver of each additive group was increased,but the difference was not significant(P>0.05),and liver mitochondrial SDH activity was significantly increased in HRC and RES groups(P<0.05),and there was a significant increase in CUR group(P=0.071).(4)Compared with the CON group,the activity of the liver mitochondrial complex Ⅰ in the HRC group was significantly increased(P<0.05),and the RES and CUR groups showed a significant increase(P=0.086),(P=0.073);Compared with the group,the activity of liver mitochondrial complex Ⅰ was significantly increased in the HRC group(P<0.05).Compared with the CON group,the activity of the complexes Ⅱ and Ⅲ of each additive group increased,but the difference was not significant(P>0.05).(4)Compared with the CON group and the ANT group,the HRC group showed a significant increase trend(P=0.080),(P=0.089).Compared with the CON group,the activity of the mitochondrial complex V in the HRC and RES groups was significantly increased(P<0.05),and there was a significant increase in the CUR group(P=0.072).(5)Compared with the CON group,the liver mtDNA copy number of the HRC group was significantly increased(P<0.05),and the difference of liver mtDNA copy number of the other additive groups was not significant(P>0.05).In summary,weaning stress can impair the growth performance,normal growth and function of the liver.Dietary addition of curcumin,resveratrol or a combination of the two can improve the growth performance,apparent digestibility of nutrients,regulate blood lipid metabolism,and increase serum antioxidant levels;can regulate liver antioxidant enzyme activity,lipid metabolism and The expression of the gene enhances the liver’s antioxidant capacity,improves liver lipid metabolism,alleviates liver damage caused by weaning stress in piglets,and promotes liver mitochondrial biosynthesis and energy metabolism,increases liver ATP content,and improves mitochondrial function.Combined with various indicators,the combination of curcumin and resveratrol,each 300 mg/kg,has the best effect,and is expected to replace dietary antibiotics in the production and application.