Effects Of Dietary Curcumin Supplementation On Liver Lipid Metabolism And RNA Methylation In LPS-Challenged-Weaned Piglets

In modern swine production,"early weaning" is used to improve sow productivity.Early weaned piglets are susceptible to immunological challenge due to their immature immune system,which would affect lipid metabolish,organ development and growth performance The liver is both metabolic and immune organ,it also plays an important role in lipid metabolism under the immunological challenge.Curcumin,a polyphenol extracted from the rhizome of Curcuma longa,has multiple properties.The aim of this study was to confirm the suitable dose of curcumin in piglet production,and then investigate effects of dietary curcumin supplementation on liver lipid metabolism,antioxidative capacity and m6A RNA methylation in LPS challenged weaned piglets,for providing a theoretical basis to the application of curcumin on piglet production.Experiment 1,effect of the various doses of dietary curcumin on growth performance,digestibility and serum parameters in weaned piglets.A total of 375 crossbred(DurocxLandrancexYorkshire)weaned piglets at the age of 28 days were randomly divided into 5 groups,with 3 replicates per group and 25 piglets per replicate,according to the body weight.The 5 groups were fed with a basal diet supplemented with 0(control group),100,200,300 and 400 mg/kg curcumin,respectively.The experiment lasted for 28 days.The results showed that compared to the control group:(1)Supplementation of 200,300 mg/kg curcumin significantlyincreased the ADG(P<0.05);Supplementation of 100,200,300,400 mg/kg curcuminsignificantly increased ADFI(P<0.05);however,varying levels of curcumin had no effects on the F/G(P>0.05).(2)Supplementation of 100,200 and 400 mg/kg curcumin increased digestibility of CP(P>0.05);supplementation of 100,200 and 400 mg/kg curcumin significantly increased digestibility of EE(P<0.05);the levels of curcumin had no effects on digestibility of DM,ash and OM(P>0.05).(3)Supplementation of 200,300 and 400 mg/kg curcumin decreased serum TC levels(P>0.05);supplementation 200 mg/kg curcumin significantly decreased serum TG levels(P<0.05);supplementation of 100,200,300 and 400 mg/kg curcumin decreased serum LDL-C levels(P>0.05).(4)Supplementation of 100,200,300 and 400 mg/kg curcumin decreased serum AST and ALT activity(P>0.05).(5)Supplementation of 300 and 400 mg/kg curcumin significantly decreased(P<0.05)serum MDA levels.Experiment 2,effects of dietary curcumin supplementation on growth performance,liver function and lipid metabolism in LPS-challenged weaned piglets.A a total of 24 Duroc X Large White X Landrace piglets were randomly assigned into 3 groups,with 8 replicates per group and 1 piglets per replicate,according to the body weight.The 3 groups are:(1)control group(Control);(2)immunological challenge group(LPS);(3)curcumin supplementation group(CurL).Piglets were fed a basal diet(Control and LPS)or basal diet supplemented with 200 mg/kg curcumin(CurL).On the 18 and 28 days of the experiment,piglets were given an intraperitoneal injection with 100 ?g/kg BW of LPS(LPS and CurL)or equivalent amount of normal saline(Control).The feeding trial was lasted for 28 d.Results showed that(1)Compared to the Control group,piglets in LPS and CurL groups had lower final body weight(P<0.05),lower ADG(P<0.05)and higher relative liver weight(P<0.05),piglets in LPS group had higher liver weight(P<0.05).(2)Compared to the Control and LPS group,piglets in the CurL group had lower serum LDH contents(P<0.05);compared to the Control group,contents of AST and LDH in the LPS and CurL group were significantly increased(P<0.05);compared to the LPS group,contents of AST and LDH in CurL group were significantly decreased(P<0.05).(3)Serum TC contents in the CurL group were much lower than the Control and LPS group(P<0.05);compared to the Control group,liver contents of TC in the LPS and CurL group were significantly increased(P<0.05);liver contents of TG in the CurL group were lower compared with the LPS group(P<0.05).(4)Compared to the LPS group,serum insulin levels in the CurL group were significantly increased(P<0.05).(5)Compared to the Control group,piglets in LPS group had lower liver FAS,INSR,IRS1 mRNA expression(P<0.05);compared with LPS group,ACC? mRNA expression in CurL group was higher(P<0.05),SCD,SREBF-1,Bcl-2 mRNA expression in CurL group were lower(P<0.05);compared with Control group,FAS,SREBF-1,INSR,IRS1,Bax,Bcl-2 mRNA expression in CurL group were significantly decreased(P<0.05),while ACC? and p53 mRNA expression in CurL group were significantly increased(P<0.05).Experiment 3,effects of dietary curcumin supplementation on liver oxidative capacity and m6A RNA methylation in LPS-challenged weaned piglets.The experiment design was the same with the experiment 2.The results showed that:(1)Severe congestion of central vein and portal area were observed in the liver of LPS group,accompanying with apparent hepatocyte vacuolation,dissolution of the hepatocyte architecture and disorganization of the parenchyma and the nuclei.Supplementaion of curcumin alleviated these pathological phenomenon.(2)Compared to the Control group,serum GSH-Px activities in LPS and CurL group were significantly increased(P<0.05),and liver SOD activity in CurL group was much higher(P<0.05).Compared to LPS group,MDA level in CurL group was significantly decreased(P<0.05).(3)Compared to the Control group,SOD1,CAT,?-catenin,Hopxy Prominin1,Bmi1,ALKBH5,FTO gene expression in the liver of LPS group were significantly decreased(P<0.05),Hsp70.Hsp90?METTL3 gene expression were significantly increased(P<0.05).Meanwhile,piglets in the.CurL group had lower SOD1,CAT,?-catenin,Hopx,Promininl,Bmi1,ALKBH5,FTO mRNA expression(P<0.05)and higher METTL3,METTL14 mRNA expression(P<0.05).Compared to the LPS group,ALKBH5 gene expression was decreased(P<0.05)and METTL14 gene expression was increased(P<0.05)in the CurL group.(4)Level of m6A in the liver of LPS group was higher than Control group(P>0.05).Level of m6A in the liver of CurL group was significantly increased compared to Control and LPS group(P<0.05).In conclusion:(1)Dietary curcumin supplementaion could improve growth performance and nutrient digestibility,decrease serum lipid metabolism,alleviate liver oxidative stress in weaned piglets,and the optimum addition of curcumin was 200 mg/kg.(2)LPS lead to poor growth performance,liver injury,lipid metabolism disorder,oxidative stress and high m6A level.On contrast,dietary curcumin supplementation could improve growth performance,promote the growing of liver,alleviate liver injury and oxidative stress,increase m6A level in LPS-challenged piglets.