Scientia Agricultura Sinica ›› 2015, Vol. 48 ›› Issue (18): 3701-3710.doi: 10.3864/j.issn.0578-1752.2015.18.013

• ANIMAL SCIENCE·VETERINARY SCIENCERE·SOURCE INSECT • Previous Articles     Next Articles

Study on the Effect of Lipopolysaccharide on Hepatic Metabolism in Dairy Goat Liver

WANG Lin-feng1, JIA Shao-dan1, YANG Gai-qing2, ZHU He-shui1, LIU Ru-yi1, YAN Ping3, LI Ming1, YANG Guo-yu1   

  1. 1 College of Animal Science and Veterinary Medicine, Henan Agricultural University/Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Zhengzhou 450002
    2Modern Experimental Technique and Managing Centre, Henan Agricultural University, Zhengzhou 450002
    3 Shangqiu Animal Disease Prevention and Control Center, Shangqiu 476000, Henan
  • Received:2014-11-19 Online:2015-09-16 Published:2015-09-16

Abstract: 【Objective】 The objective of this experiment is to study the effect of lipopolysaccharide (LPS) on metabolism of dairy goat liver, explore the characteristic metabolites in the liver and clarify the mechanism of hepatic dysbolism caused by LPS.【Method】Total 15 Guanzhong dairy goats of 12-month-old with 24-28 kg live body weight (BW) were selected and divided into three groups randomly, i.e. control group (CTL, goat No. 1-5), LPS-L group (LPS-L, goat No. 6-10) and LPS-H group (LPS-H, goat No.11-15). Animals were fed total mixed ration (TMR) made according to NRC (2007). The experimental goats were fed with feeds and water ad libitum. After 14d adaption, the experiment was conducted. At the beginning of the experiment (0 h), the goats in LPS-L and LPS-H were given 20 and 40μg·kg-1 BW of LPS solution via intraperitoneal injections, respectively. The goats in CTL were received same volume of saline water. 24 h later, goats in each LPS treatment groups were added LPS solution once again. 48 h later from the beginning, blood samples were drawn from jugular vein and were centrifuged to extract plasma for biochemical determination. Subsequently, the goats’ liver tissue samples were collected by biopsy and marked and stored in liquid nitrogen. 1H-NMR metabonomics was used to research the changes of metabolites in goat liver, the obtained metabolites. The data variables (concentration value of metabolites) were analyzed by the software of partial least squares discriminant analysis (PLS-DA) installed in the equipment to identify metabolic differences between the groups of each treatment. 【Result】Serum biochemical results showed that the concentration of ALT, AST and TBIL increased significantly, while TG, TC, VLDL, NEFA, HDL, LDL, ALB, TP decreased to different degrees in LPS treated groups compared with that of CTL, indicating the goats liver were injured to some degrees and the dysbolism was occurred in goat liver. With the 1H-NMR metabonomics determination, totally 69 metabolites were detectedbased on its identification database of Chenomx. After the metabolite variables analyzing using PLS-DA, it showed that the CTL, LPS-L and LPS-H groups could be clustered and distinguished based on the metabolomic data analysis. Nine out of 69 metabolites differed significantly among the three groups. Based on the statistics and analysis between any two of the groups, 6 metabolites located in LPS-L and LPS-H groups were notable compared with the CTL, and 3 metabolites were different significantly between LPS-L and LPS-H. Further analysis indicated that these metabolites were related to amino acid metabolism, fat metabolism and carbohydrate metabolism in the liver.【Conclusion】In conclusion, LPS induced significant changes in liver reflected in blood biochemical indices. Metabolomics profile could precisely detect characteristic metabolites and effectively distinguish LPS-L and LPS-H from CTL effectively. Metabolomic technology could clarify the mechanism for liver dysbolism suffering from LPS and provide enough information to diagnose liver injury via analyzing the relevant pathway.

Key words: metabolomics, lipopolysaccharide, liver, metabolite, dairy goat

[1]    Garcia-Lazaro J F, Thieringer F, Luth S, Czochra P, Meyer E, Renteria I B, Galle P R, Lohse A W, Herkel J, Kanzler S. Hepatic over-expression of TGF-beta1 promotes LPS-induced inflammatory cytokine secretion by liver cells and endotoxemic shock. Immunology Letters, 2005, 101(2):217-222.
[2]    Khafipour E, Krause D O, Plaizier J C. A grain-based subacute ruminal acidosis challenge causes translocation of lipopolysaccharide and triggers inflammation. Journal of Dairy Science, 2009, 92(3): 1060-1070.
[3]    Nolan J P. The role of endotoxin in liver injury. Gastroenterology, 1975, 69(6):1346-1356.
[4]    Fukui H, Brauner B, Bode J C, Bode C. Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay. Journal of Hepatology, 1991, 12(2):162-169.
[5]    Su G L. Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation. American Journal of Physiology- Gastrointestinal And Liver Physiology, 2002, 283(2): G256-G265.
[6]    Yamada H, Arai T, Endo N, Yamashita K, Fukuda K, Sasada M, Uchiyama T. LPS-induced ROS generation and changes in glutathione level and their relation to the maturation of human monocyte-derived dendritic cells. Life Sciences, 2006, 78(9):926-933.
[7]    Yang S Q, Lin H Z, Lane M D, Clemens M, Diehl A M. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proceedings of the National Academy of Sciences, 1997, 94(6):2557-2562.
[8]    Knoll P, Schlaak J, Uhrig A, Kempf P, Zum Büschenfelde K M, Gerken G. Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge. Journal of Hepatology, 1995, 22(2): 226-229.
[9]    Karin M, Greten F R. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nature Reviews Immunology, 2005, 5(10):749-759.
[10]   Masaki T, Chiba S, Tatsukawa H, Yasuda T, Noguchi H, Seike M, Yoshimatsu H. Adiponectin protects LPS‐induced liver injury through modulation of TNF‐α in KK‐Ay obese mice. Hepatology, 2004, 40(1):177-184.
[11]   Novogrodsky A, Vanichkin A, Patya M, Gazit A, Osherov N, Levitzki A. Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors. Science, 1994, 264(5163):1319-1322.
[12]   Pan M, Lai C, Wang Y, Ho C. Acacetin suppressed LPS-induced up-expression of iNOS and COX-2 in murine macrophages and TPA-induced tumor promotion in mice. Biochemical Pharmacology, 2006, 72(10):1293-1303.
[13]   Nowak M, Gaines G C, Rosenberg J, Minter R, Bahjat F R, Rectenwald J, MacKay S L, Edwards III C K, Moldawer L L. LPS-induced liver injury ind-galactosamine-sensitized mice requires secreted TNF-α and the TNF-p55 receptor. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2000, 278(5): R1202-R1209.
[14]   Osorio M T, Moloney A P, Brennan L, Monahan F J. Authentication of beef production systems using a metabolomic-based approach. Animal, 2012, 6(01):167-172.
[15]   Lindon J C, Holmes E, Bollard M E, Stanley E G, Nicholson J K. Metabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis. Biomarkers, 2004, 9(1):1-31.
[16]   Brindle J T, Antti H, Holmes E, Tranter G, Nicholson J K, Bethell H W, Clarke S, Schofield P M, McKilligin E, Mosedale D E. Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics. Nature Medicine, 2002, 8(12):1439-1445.
[17] National Research Council (NRC). Nutrient requirements of small ruminants: sheep, goats, cervids, and new world camelids. Committee on the nutrient requirements of small ruminants, Washington D C: The National Academies Press, 2007: 235-236.
[18]   Swanson K S, Merchen N R, Erdman J J, Drackley J K, Orias F, Douglas G N, Huhn J C. Technical note: a technique for multiple liver biopsies in neonatal calves. Journal of Animal Science, 2000, 78(9):2459-2463.
[19]   齐海宇, 肖红丽, 阴赪宏, 王宝恩. 内毒素血症急性肝损伤的特点及致病机制. 中国中西医结合急救杂志, 2014, 21(2):144-146.
Qi H Y,Xiao H L,Yin Z H,Wang B E. Characteristics and pathogenic mechanism of endotoxemia induced acute hepatic injury. Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care, 2014, 21(2):144-146. (in Chinese)
[20]   Milagro F I, Campion J, Martinez J A. Weight gain induced by high-fat feeding involves increased liver oxidative stress. Obesity (Silver Spring), 2006,14(7):1118-1123.
[21]   董晓玲, 刘国华, 蔡辉益, 郑爱娟, 张姝, 陈桂兰, 李勇, 常文环. 细菌脂多糖诱导的急性免疫应激对肉仔鸡肉品质的影响. 动物营养学报, 2007, 19(5):622-626.
Dong X L, Liu G H, Cai H Y, Zheng A J, Zhang S, Chen G L, Li Y, Chang W H. Effect of acute immunological stress induced by LPS on meat quality of broiler. Chinese Journal of Animal Nutrition, 2007, 19(5):622-626. (in Chinese)
[22]   王林枫, 赵志伟, 杨改青, 王月影, 朱河水, 韩立强, 张震, 杨国宇. 急性内毒素损伤对奶山羊肝脏营养代谢的影响. 动物营养学报, 2012, 24(12):2366-2374.
Wang L F, Zhao Z W, Yang G Q, Wang Y Y, Zhu H S,Han L Q, Zhang Z, Yang G Y. Effects of acute lipopolysaccharide injuryon liver nutrition metabolismindairy goats. Chinese Journal of Animal Nutrition, 2012, 24(12):2366-2374. (in Chinese)
[23]   Zebeli Q, Dunn S M, Ametaj B N. Perturbations of plasma metabolites correlated with the rise of rumen endotoxin in dairy cows fed diets rich in easily degradable carbonhydrates. Journal of Dairy Science, 2011, 94(5):2374-2382.
[24]   Waldron M R, Nishida T, Nonnecke B J, Overton T R. Effect of lipopolysaccharide on indices of peripheral and hepatic metabolism in lactating cows. Journal of Dairy Science, 2003, 86(11):3447-3459.
[25]   黄燕, 刘培庆. 烟酸受体GPR109A介导的烟酸作用机制研究进展. 中国药理学与毒理学杂志, 2012, 26 (1):105-107.
Huang Y, Liu P Q. Progress in mechanism of nicotinic acid mediated by nicotinic acid receptor GPR109. Chinese Journal of Pharmacology and Toxicology, 2012, 26 (1):105-107. (in Chinese)
[26]   Wu G, Fang Y, Yang S, Lupton J R, Turner N D. Glutathione metabolism and its implications for health. The Journal of nutrition, 2004, 134(3):489-492.
[27]   Merry T L, Tran M, Stathopoulos M, Wiede F, Fam B C, Dodd G T, Clarke I, Watt M J, Andrikopoulos S, Tiganis T. High-fat-fed obese glutathione peroxidase 1-deficient mice exhibit defective insulin secretion but protection from hepatic steatosis and liver damage. Antioxid Redox Signal, 2014, 20(14):2114-2129.
[28]   Grimble R F, Grimble G K. Immunonutrition: role of sulfur amino acids, related amino acids, and polyamines. Nutrition, 1998, 14(7):605-610.
[29]   Yokogoshi H, Mochizuki H, Nanami K, Hida Y, Miyachi F, Oda H. Dietary taurine enhances cholesterol degradation and reduces serum and liver cholesterol concentrations in rats fed a high-cholesterol diet. Journal of Nutrition, 1999, 129(9):1705-1712.
[30]   Zhang M, Bi L F, Fang J H, Su X L, Da G L, Kuwamori T, Kagamimori S. Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects. Amino Acids, 2004, 26(3):267-271.
[1] YUE LiXin, WANG QingHua, WANG ZhenBao, NIMAQIONGJI, LIU ZeZhou, KONG SuPing, ZHANG LiFeng, GAO LiMin. Widely Targeted Metabolomics-Based Analysis of the Differences in Tibetan Bunching Onion and Chive on Nutritional Quality and Flavonoid Metabolites [J]. Scientia Agricultura Sinica, 2026, 59(5): 1070-1086.
[2] TAN XiBei, LAN XuYing, LIU ChongHuai, FAN XiuCai, JIANG JianFu, SUN Lei, LI Peng, YU ShuXin, ZHANG Ying. Changes of Secondary Metabolites in Grapes with Different Resistance Levels in Response to White Rot Infection [J]. Scientia Agricultura Sinica, 2025, 58(9): 1767-1778.
[3] YANG CaiLi, LI YongZhou, HE LiangLiang, SONG YinHua, ZHANG Peng, LIU ZhaoXian, LI PengHui, LIU SanJun. Genome-Wide Identification and Analysis of TPS Gene Family and Functional Verification of VvTPS4 in the Formation of Monoterpenes in Grape [J]. Scientia Agricultura Sinica, 2025, 58(7): 1397-1417.
[4] JU XiaoJun, ZHANG Ming, LIU YiFan, JI GaiGe, SHAN YanJu, TU YunJie, ZOU JianMin, ZHANG HaiTao, BIAN LiangYong, SHU JingTing. Integration of Intestinal Flora and Small Molecule Metabolite to Analyze the Role of Factors Regulating Feed Conversion in Broiler Chickens [J]. Scientia Agricultura Sinica, 2025, 58(6): 1223-1238.
[5] LUO ChaoDan, FENG ChunMei, LI JianQiang, LI XinRong, WEI Yong, YANG LiYi, LIU XiaoJin, TAN He, REN ErFang, LUO XiaoJie. Analysis of Differential Aroma Volatiles of Tainong No.1 Mango of Different Ripeness by Non-Targeted Metabolomics Based on Gas Chromatography-Mass Spectrometry [J]. Scientia Agricultura Sinica, 2025, 58(3): 564-581.
[6] LUO Qin, CHEN XieYong, XU YuYing, WEI Hang, HUANG Biao, YAO QingHua, YE NaiXing, ZHENG DeYong, YAN MingJuan. Characterization of Non-Volatile Metabolites of White Peony Tea Make of Camellia sinensis Fu’an-dabaicha from Different Origins [J]. Scientia Agricultura Sinica, 2025, 58(22): 4757-4770.
[7] ZHAN Li, LIANG ZongSuo, YU Jing, LU Jun, LIANG Qian. Insecticidal Active Component Identification of Camellia oleifera Shell Against Mythimna separata and Its Action Mechanism [J]. Scientia Agricultura Sinica, 2025, 58(13): 2591-2603.
[8] XIE Qian, JIANG Lai, DING MingYue, LIU LingLing, CHEN QingXi. Metabolomic Analysis of Canarium album Fresh Food Quality Differences Based on Sensory Evaluation [J]. Scientia Agricultura Sinica, 2024, 57(2): 363-378.
[9] QI XiaoYu, KONG XiaoPing, ZHOU HongWei, YAN XiangPing. Crucial Factors Impacting Carrot Flavor Analysis Based on Broad Target Metabolomics [J]. Scientia Agricultura Sinica, 2024, 57(16): 3250-3263.
[10] GAO ChengAn, WAN HongJian, YE QingJing, CHENG Yuan, LIU ChenXu, HE Yong. Identification and Comparative Analysis of Processed/Fresh-Eating Chili Pepper Fruits at Different Maturation Stages by Metabolomics [J]. Scientia Agricultura Sinica, 2024, 57(12): 2424-2438.
[11] GUO RongKun, DONG NingGuang, NONG HuiLan, WANG Han, TENG WeiChao, MENG JiaXin. Targeted Metabolomics-Based Analysis of Peel Color Differences Between Yellow and Red Hawthorn [J]. Scientia Agricultura Sinica, 2024, 57(12): 2439-2453.
[12] CAI RuiJie, CHU YiXin, SHI XinE, JIN JianJun, YANG GongShe. Dietary Addition of Cordyceps Militaris Can Alleviate Lipopolysaccharide- Induced Liver Damage and Skeletal Muscle Protein Degradation in Early Weaning Piglets [J]. Scientia Agricultura Sinica, 2024, 57(12): 2467-2482.
[13] WU YaNuo, LIU Yuan, KONG JiaTao, HU ZheHui, CHEN MingHua, WU JunChen, ZHANG HongYan, JIANG YouWu, XU Juan, CHEN JiaJing. Basing Fuzzy Modeling to Evaluate Sensory Quality Differences of ‘Orah’ Mandarin Fruits from Various Production Regions [J]. Scientia Agricultura Sinica, 2024, 57(10): 2010-2022.
[14] SHENG HongJie, LU SuWen, ZHENG XuanAng, JIA HaiFeng, FANG JingGui. Identification and Comparative Analysis of Metabolites in Grape Seed Based on Widely Targeted Metabolomics [J]. Scientia Agricultura Sinica, 2023, 56(7): 1359-1376.
[15] LIU Chang, CUI ZiXu, ZUO Zhou, YUN HongMei, NIU Jin, YANG Yang, GUO XiaoHong, LI BuGao, GAO PengFei, ZHAO Yan, CAO GuoQing. Effects of Dietary Fiber Level on Intestinal Barrier Function, Colonic Microbiota and Metabolites in Pigs [J]. Scientia Agricultura Sinica, 2023, 56(22): 4532-4551.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!