Effects of Grape Seed Proanthocyanidins on Liver Inflammation and Antioxidant Function of Fattening Sheep Fed a High-Concentrate Diet and Metabolomic Analysis
The aim of this study was to investigate the effects of grape seed proanthocyanidins(GSPs)on liver morphological structure,liver function,antioxidant capacity and inflammatory response of sheep fed a high-concentrate diet,and analyze liver metabolic changes using non-targeted metabolomics.A total of forty-eight 4-month-old Dorper×thin-tailed Han ram lambs with similar body weight[(22.75±1.20)kg]were fed a 70:30 concentrate:forage basal diet and randomly assigned to one of four groups of 12 lambs each.The basal diet supplemented with 0(control group),10(10GSPs group),20(20GSPs group),or 40 mg/kg BW GSPs(40GSPs group)per day.The experimental sheep were raised in a single pen and fed freely with diets and wa-ter.The experiment lasted for 60 days,including 15 days of pre-test.The results showed as follows:1)the hepatocytes swelling and vacuolation were severe in the control group,while the damage of liver tissue in each GSPs supplementation group was alleviated to different degrees.2)The contents of serum total protein and al-bumin were linearly increased(P<0.05),while the activities of serum aspartate aminotransferase and glutami-notransferase were linearly decreased(P<0.05).The total antioxidant capacity(T-AOC)of liver showed a quadratic curve,the activity of glutathione peroxidase(GSH-Px)increased linearly,and the content of malon-dialdehyde(MDA)decreased linearly(P<0.05).The activity of myeloperoxidase(MPO)in liver was linear-ly decreased,and the contents of inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were linearly decreased(P<0.05).Compared with control group,serum li-popolysaccharide(LPS)and lipopolysaccharids-binding protein(LBP)contents in MGSPs and HGSPs groups were significantly decreased(P<0.05).3)With the increase of GSPs supplemental level,the contents of tri-glyceride,total cholesterol and low density lipoprotein cholesterol in liver were linearly decreased(P<0.05).4)The non-targeted metabolomics results showed that there were a total of 99 different metabolites between the MGSPs group and the control group,including 67 lipid substances.Among the 99 kinds of metabolites,71 were significantly up-regulated and 28 were significantly down-regulated.Differential metabolites were enriched in choline metabolism in cancer,glycerophospholipid metabolism,retrograde endocannabinoid signaling,auto-phagy-other/animal and other potential target pathways.In conclusion,GSPs can improve the antioxidant ca-pacity of liver of sheep fed a high-concentrate diet,reduce the contents of inflammatory factors.It may alleviate inflammatory damage through regulating liver lipid metabolism,choline metabolism,and liver cell autophagy to jointly respond to liver inflammatory response and oxidative stress.[Chinese Journal of Animal Nutrition,2024,36(7):4447-4461]