| In the current intensive culture mode,many factors can lead to oxidative stress in piglets.Oxidative stress causes lipid metabolism disorder,increased de novo lipogenesis,which will increase liver load and affect growth performance of piglets.In order to study the effect and mechanism of garcinol regulating lipogenesis in liver of piglets under oxidative stress,this experiment was verified by in vitro and in vivo experiment.Thirty35-day-old piglets with healthy condition and similar parity were randomly divided into five groups,including control group,oxidative stress group,200 mg/kg garcinol group,400 mg/kg garcinol group and 600 mg/kg garcinol group.There are 6 replicates in each group and 1 piglet in each replicate.After 7 days of pre-feeding,the formal trial was started.The experiment lasted for 28 days.The stress group and the garcinol groups were injected with diquat on the 15 th day of the experiment,and the garcinol groups were fed the garcinol from the first day of the experiment until the end of the experiment.Hepatocytes of 5?7 days old piglets were isolated and divided into 5 groups,including control group,stress group,5 ?M garcinol group,10 ?M garcinol group and 20 ?M garcinol group to explore the role and mechanism of garcinol in regulating liver lipid synthesis in pig under oxidative stress.The stress group and the garcinol groups treated the cells with 400 ?mol/L hydrogen peroxide for 2 h to construct the oxidative stress model.The main findings are as follows:(1)The results of growth performance and antioxidant index revealed that the average daily gain(ADG)and average daily feed intake(ADFI)of piglets in the oxidative stress group were significantly lower than those in the control group(P < 0.05),the feed/gain(F/G)was significantly higher than that in the control group(P < 0.05),and the ADG and ADFI in the garcinol group were significantly higher than those in the stress group(P < 0.05).Garcinol significantly increased superoxide dismutase(SOD)activity and total antioxidant capacity(T-AOC)content in normal piglets(P < 0.05).The activity of SOD and glutathione peroxidase(GSH-Px)in serum and liver of the oxidative stress group was significantly lower than that of the control group(P < 0.05),and the content of malondialdehyde(MDA)was significantly higher than that of the control group(P <0.05).Dietary garcinol supplement significantly increased the activity of SOD and GSH-Px in serum and liver of piglets in the stress group(P<0.05),and significantly decreased the content of MDA(P<0.05).(2)The results of liver histology and lipid content detection showed that compared with the control group,the liver tissue structure of the oxidative stress group was damaged,and lipid deposition in the liver was significantly increased,and the serum and liver triglyceride(TG)content was significantly increased(P < 0.05).The liver tissue structure of the garcinol group recovered to a certain extent compared with the stress group.In addition,lipid deposition was also significantly reduced,and the serum and liver triglyceride(TG)content was significantly reduced(P < 0.05).The effect was best when the dosage was 600 mg/kg.(3)The expression of genes related to lipid synthesis and PCAF gene showed that compared with the control group,the m RNA expression levels of SREBP-1c,FAS,ACC and SCD1 in the stress group were significantly increased(P < 0.05).Compared with the stress group,the m RNA expression of SREBP-1c and ACC in the 200 mg/kg garcinol group were significantly decreased(P < 0.05).The m RNA expression of SREBP-1c,FAS,SCD1 and ACC in the 400 mg/kg garcinol group were significantly decreased(P < 0.05).The m RNA expression of SREBP-1c,FAS and ACC in the 600 mg/kg garcinol group were significantly decreased(P < 0.05).There was no significant difference among the three garcinol groups.PCAF gene expression results showed that oxidative stress significantly increased the expression of PCAF(P < 0.05),and the addition of garcinol to the diet significantly inhibited the expression of PCAF(P < 0.05).The inhibitory effect became stronger with the increase of garcinol.(4)Cell experiment results showed that TG content in hepatocytes in the stress group was extremely significantly higher than that in the control group(P < 0.01),while TG content in hepatocytes in the garcinol group was significantly lower than that in the stress group(P < 0.05),which was dose-dependent.TG content in hepatocytes decreased continuously with the increase of garcinol concentration.The results of lipid synthesis gene expression showed that compared with the control group,the gene expression of FAS,ACC,SCD1,and SREBP-1c in the stress group was significantly increased(P <0.05).Compared with the stress group,the gene expression of SREBP-1c was significantly reduced in the low concentration of garcinol(P<0.05),the gene expression of the FAS,ACC,SREBP-1c was significantly reduced in the medium concentration of garcinol(P<0.05),the gene expression of the FAS,ACC,SCD1,SREBP-1c was significantly reduced in the high concentration of garcinol(P<0.05).The results of PCAF expression and co-immunoprecipitation showed that compared with the cells in the control group,the PCAF gene expression in the oxidative stress group increased significantly(P<0.05),and the level of USF-1 acetylation increased significantly.Compared with the stress group,the PCAF expression and USF-1 acetylation level in the different concentration of garcinol group was significantly reduced(P<0.05).As the concentration of garcinol increased,PCAF expression and USF-1 acetylation level decreased.In conclusion,dietary garcinol can improve the antioxidant capacity of the piglets,alleviate oxidative stress and improve the growth performance of stressed piglets.Garcinol can regulate the acetylation level of USF-1 by inhibiting the expression of PCAF,through the PCAF/USF-1 pathway to regulate liver lipid synthesis under oxidative stress,reducing lipid deposition,and protecting the integrity of liver structure and function. |
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