Effects Of α-lipoic Acid On Growth Performance,Antioxidant Capacity And Immune Function In Sheep And Its Mechanism

The sheep production performance and meat quality were partly influenced by various stressors,such as heat or cold stress,feeding density,oxidative stress,and diseases.The previously research had reported that α-LA could reduce oxidative damage and inflammation of host by removing ROS,chelating metal ions and regenerating endogenous antioxidants to improve its antioxidant capacity.Therefore,the purpose of this study was to investigate the growth performance,antioxidant capacity and immune function in sheep with different levels of α-LA supplemented in diet.This research will provide certain contribution for the effective utilization of α-LA in sheep production.The study was divided into two parts:Experiment 1: Effects of α-lipoic acid on growth performance,antioxidant capacity and immune function in sheep.One hundred Duhu F1 hybrid(Dupo♀ × Hu sheep♂)sheep aged 2 ~ 3 months with similar body weight(27.49 ± 2.10kg)were randomly allocated into 5 groups,five diets supplemented with 0(CTL),300(LA300),450(LA450),600(LA600),and 750(LA750)mg/kg α-LA were fed to sheep.Feeding twice a day(07:00;16:00),each sheep was free to drink and exercise.The pre-trial lasted for 7 days and the trial lasted for 60 days.Feed intake,body weight and slaughter indexes of sheep were recorded,blood and rumen epithelium,liver,ileum,muscle tissues samples were collected,and detected antioxidant and immune indexes of serum and tissues.The results show that:(1)Compared with CTL group,α-LA supplementation significantly increased the average daily feed intake(P < 0.05).Tare weight in LA750 group was significantly decreased(P < 0.05).The small intestine weight in LA450 group was significantly increased(P < 0.05).However no significant variation was found in the average daily gain,feed conversion rate,carcass weight and slaughter rate among groups(P > 0.05).(2)Compared with CTL group,SOD,CAT and GSH-Px activities in serum of LA600 and LA750 groups were increased(P < 0.05).At LA450-LA750 groups,SOD,CAT activities in liver and ileum tissues and GSH-Px activities in ileum tissues were increased than CTL group(P < 0.05),while MDA contents in serum and muscle tissue were decreased than CTL group(P < 0.05).The T-AOC contents in liver,muscle and ileum tissues of LA600 group were increased compared with CTL group(P < 0.05).(3)Compared with CTL group,the IL-10 contents of serum in LA450 ~ LA750 groups were increased than CTL group(P < 0.05),the contents of IL-1β in serum,IL-2 in liver,and IL-6,IL-1β in muscle were decreased than CTL group(P < 0.05).The content of Ig A in serum of LA600 group,ileum and muscle of LA750 group were increased than CTL group(P < 0.05).Experiment 2: Effects of α-LA on rumen epithelial tissue metabolism and transcription in sheep.Based on experiment 1,rumen epithelial tissues of CTL group and LA600 group were selected for metabolome and transcriptome analysis.The results show that:(1)Metabolomics results showed that,compared with CTL group,α-LA supplementation of 600 mg/kg affected the ferroptosis and cytochrome P450 metabolism of foreign substances,glycerol phospholipid metabolism,amino acid metabolism and nucleotide metabolism pathways of rumen epithelial tissue.(2)Transcriptomics results showed that compared with CTL group,α-LA supplemented with 600 mg/kg diet regulated rumen growth and development by affecting metabolically related pathways such as steroid hormone synthesis,alanine,aspartic acid and glutamate metabolism,nitrogen metabolism,protein processing in endoplasmic reticulum,ABC transporter,PPAR signaling pathway,etc.Meanwhile,α-LA also regulates the immune response and inflammatory response of rumen epithelium by affecting immune-related pathways such as antigen processing and presentation,phagosomes,cell adhesion molecules,and MAPK signaling pathways.Conclusions: The addition of α-LA to the diet increased sheep feed intake and enhanced the antioxidant capacity and immune function of sheep serum and tissues.α-LA improved the antioxidant capacity of the rumen epithelium through the pathways of ferroptosis and cytochrome P450 metabolism of foreign substances,regulated the growth and development of the rumen through the pathways of glycerophospholipid metabolism,nucleotide metabolism,protein synthesis and processing.Regulated the rumen epithelium of immune response capacity through antigen processing and presentation,phagocytic vesicles,cell adhesion molecules,and MAPK signaling pathway.