Abstract
Purpose
The present study investigated whether dietary methionine supplementation might protect against intrauterine growth retardation (IUGR)-induced damage in the intestine of piglets.
Methods
Thirty normal birth weight (NBW) female piglets and sixty same-sex IUGR piglets were weaned at 21 days of postnatal age and fed the control diet (4.0 g methionine per kg of feed, NBW-CON, and IUGR-CON groups) or the methionine-supplemented diet (5.2 g methionine per kg of feed, IUGR-MET group) for 28 days (n = 6).
Results
Piglets in the IUGR-CON group showed decreased average daily feed intake and average daily gain and an increased feed conversion ratio than those in the NBW-CON group. Compared with NBW-CON piglets, IUGR-CON piglets had decreased villus height (VH) and villus height-to-crypt depth ratio in both the jejunum and ileum. In addition, in comparison with the NBW-CON piglets, IUGR increased the concentration of malondialdehyde (MDA) and the index of apoptosis, while it decreased the concentrations of methionine and reduced glutathione (GSH), the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG), and the protein expression of occludin (OCLN) in both the jejunum and ileum. Dietary methionine supplementation decreased the MDA and protein carbonyl concentrations and the apoptotic index, while it increased the VH level, methionine and GSH concentrations, GSH/GSSG ratio, and the OCLN protein expression in the jejunum of IUGR-MET piglets.
Conclusions
Methionine may have beneficial effects in improving intestinal integrity and oxidative status in IUGR weanling piglets.
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References
Xita N, Tsatsoulis A (2010) Fetal origins of the metabolic syndrome. Ann N Y Acad Sci 1205:148–155. doi:10.1111/j.1749-6632.2010.05658.x
Ogata ES, Bussey ME, Finley S (1986) Altered gas exchange, limited glucose and branched chain amino acids, and hypoinsulinism retard fetal growth in the rat. Metabolism 35:970–977
Hales CN, Barker DJP (1992) Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35:595–601
Wu G (1998) Intestinal mucosal amino acid catabolism. J Nutr 128:1249–1252
Dong L, Zhong X, Ahmad H, Li W, Wang Y, Zhang L, Wang T (2014) Intrauterine growth restriction impairs small intestinal mucosal immunity in neonatal piglets. J Histochem Cytochem 62:510–518. doi:10.1369/0022155414532655
Wang Y, Zhang L, Zhou G, Liao Z, Ahmad H, Liu W, Wang T (2012) Dietary l-arginine supplementation improves the intestinal development through increasing mucosal Akt and mammalian target of rapamycin signals in intra-uterine growth retarded piglets. Br J Nutr 108:1371–1381. doi:10.1017/S0007114511006763
Wang X, Wu W, Lin G, Li D, Wu G, Wang J (2010) Temporal proteomic analysis reveals continuous impairment of intestinal development in neonatal piglets with intrauterine growth restriction. J Proteome Res 9:924–935. doi:10.1021/pr900747d
Maeda T, Miyazono Y, Ito K, Hamada K, Sekine S, Horie T (2010) Oxidative stress and enhanced paracellular permeability in the small intestine of methotrexate-treated rats. Cancer Chemother Pharmacol 65:1117–1123. doi:10.1007/s00280-009-1119-1
Sheth P, Basuroy S, Li C, Naren AP, Rao RK (2003) Role of phosphatidylinositol 3-kinase in oxidative stress-induced disruption of tight junctions. J Biol Chem 278:49239–49245. doi:10.1074/jbc.M305654200
Tesseraud S, Métayer Coustard S, Collin A, Seiliez I (2009) Role of sulfur amino acids in controlling nutrient metabolism and cell functions: implications for nutrition. Br J Nutr 101:1132–1139. doi:10.1017/S0007114508159025
Chen Y, Li D, Dai Z, Piao X, Wu Z, Wang B, Zhu Y, Zeng Z (2014) l-Methionine supplementation maintains the integrity and barrier function of the small-intestinal mucosa in post-weaning piglets. Amino Acids 46:1131–1142. doi:10.1007/s00726-014-1675-5
Xu W, Bai K, He J, Su W, Dong L, Zhang L, Wang T (2016) Leucine improves growth performance of intrauterine growth retardation piglets by modifying gene and protein expression related to protein synthesis. Nutrition 32:114–121. doi:10.1016/j.nut.2015.07.003
Zhang H, Chen Y, Li Y, Yang L, Wang J, Wang T (2014) Medium-chain TAG attenuate hepatic oxidative damage in intra-uterine growth-retarded weanling piglets by improving the metabolic efficiency of the glutathione redox cycle. Br J Nutr 112:876–885. doi:10.1017/S000711451400155X
Conde-Aguilera JA, Le Floc’h N, Le Huërou-Luron I, Mercier Y, Tesseraud S, Lefaucheur L, van Milgen J (2016) Splanchnic tissues respond differently when piglets are offered a diet 30% deficient in total sulfur amino acid for 10 days. Eur J Nutr 55:2209–2219. doi:10.1007/s00394-015-1031-x
Bauchart-Thevret C, Stoll B, Chacko S, Burrin DG (2009) Sulfur amino acid deficiency upregulates intestinal methionine cycle activity and suppresses epithelial growth in neonatal pigs. Am J Physiol Endocrinol Metab 296:E1239–E1250. doi:10.1152/ajpendo.91021.2008
Deng QH, Jia G, Zhao H, Chen ZL, Chen XL, Liu GM, Wang KN (2016) The prolonged effect of glucagon-like peptide 2 pretreatment on growth performance and intestinal development of weaned piglets. J Anim Sci Biotechnol 7:28. doi:10.1186/s40104-016-0087-7
Tang Z, Yin Y, Zhang Y, Huang R, Sun Z, Li T, Chu W, Kong X, Li L, Geng M, Tu Q (2009) Effects of dietary supplementation with an expressed fusion peptide bovine lactoferricin–lactoferrampin on performance, immune function and intestinal mucosal morphology in piglets weaned at age 21 d. Br J Nutr 101:998–1005. doi:10.1017/S0007114508055633
Zhu L, Cai X, Guo Q, Chen X, Zhu S, Xu J (2013) Effect of N-acetyl cysteine on enterocyte apoptosis and intracellular signalling pathways’ response to oxidative stress in weaned piglets. Br J Nutr 110:1938–1947. doi:10.1017/S0007114513001608
Ferenc K, Pietrzak P, Godlewski MM, Piwowarski J, Kiliańczyk R, Guilloteau P, Zabielski R (2014) Intrauterine growth retarded piglet as a model for humans—studies on the perinatal development of the gut structure and function. Reprod Biol 14:51–60. doi:10.1016/j.repbio.2014.01.005
Wang T, Huo YJ, Shi F, Xu RJ, Hutz RJ (2005) Effects of intrauterine growth retardation on development of the gastrointestinal tract in neonatal pigs. Biol Neonate 88:66–72. doi:10.1159/000084645
D’Inca R, Kloareg M, Gras-Le Guen C, Le Huërou-Luron I (2010) Intrauterine growth restriction modifies the developmental pattern of intestinal structure, transcriptomic profile, and bacterial colonization in neonatal pigs. J Nutr 140:925–931. doi:10.3945/jn.109.116822
National Research Council (2012) Nutrient requirements of swine, 11th edn. National Academy Press, Washington, DC
Moore S, Stein WH (1963) [117] Chromatographic determination of amino acids by the use of automatic recording equipment. Methods Enzymol 6:819–831
Dong L, Zhong X, He J, Zhang L, Bai K, Xu W, Wang T, Huang X (2016) Supplementation of tributyrin improves the growth and intestinal digestive and barrier functions in intrauterine growth-restricted piglets. Clin Nutr 35:399–407. doi:10.1016/j.clnu.2015.03.002
Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45
van de Poll MC, Dejong CH, Soeters PB (2006) Adequate range for sulfur-containing amino acids and biomarkers for their excess: lessons from enteral and parenteral nutrition. J Nutr 136:1694S–1700S
Métayer S, Seiliez I, Collin A, Duchêne S, Mercier Y, Geraert PA, Tesseraud S (2008) Mechanisms through which sulfur amino acids control protein metabolism and oxidative status. J Nutr Biochem 19:207–215. doi:10.1016/j.jnutbio.2007.05.006
Mastrototaro L, Sponder G, Saremi B, Aschenbach JR (2016) Gastrointestinal methionine shuttle: priority handling of precious goods. IUBMB Life 68:924–934. doi:10.1002/iub.1571
Han F, Hu L, Xuan Y, Ding X, Luo Y, Bai S, He S, Zhang K, Che L (2013) Effects of high nutrient intake on the growth performance, intestinal morphology and immune function of neonatal intra-uterine growth-retarded pigs. Br J Nutr 110:1819–1827. doi:10.1017/S0007114513001232
Wang W, Degroote J, Van Ginneken C, Van Poucke M, Vergauwen H, Dam TM, Vanrompay D, Peelman LJ, De Smet S, Michiels J (2016) Intrauterine growth restriction in neonatal piglets affects small intestinal mucosal permeability and mRNA expression of redox-sensitive genes. FASEB J 30:863–873. doi:10.1096/fj.15-274779
Wang WW, Qiao SY, Li DF (2009) Amino acids and gut function. Amino Acids 37:105–110. doi:10.1007/s00726-008-0152-4
Montagne L, Pluske JR, Hampson DJ (2003) A review of interactions between dietary fibre and the intestinal mucosa, and their consequences on digestive health in young non-ruminant animals. Anim Feed Sci Technol 108:95–117. doi:10.1016/S0377-8401(03)00163-9
Walsh SV, Hopkins AM, Nusrat A (2000) Modulation of tight junction structure and function by cytokines. Adv Drug Deliv Rev 41:303–313
Cummins AG, Steele TW, Labrooy JT, Shearman DJ (1988) Maturation of the rat small intestine at weaning: changes in epithelial cell kinetics, bacterial flora, and mucosal immune activity. Gut 29:1672–1679
Buchmiller-Crair TL, Gregg JP, Rivera FA Jr, Choi RS, Diamond JM, Fonkalsrud EW (2001) Delayed disaccharidase development in a rabbit model of intrauterine growth retardation. Pediatr Res 50:520–524. doi:10.1203/00006450-200110000-00016
D’Inca R, Gras-Le Guen C, Che L, Sangild PT, Le Huërou-Luron I (2010) Intrauterine growth restriction delays feeding-induced gut adaptation in term newborn pigs. Neonatology 99:208–216. doi:10.1159/000314919
Günther C, Neumann H, Neurath MF, Becker C (2013) Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium. Gut 62:1062–1071. doi:10.1136/gutjnl-2011-301364
Baserga M, Bertolotto C, Maclennan NK, Hsu JL, Pham T, Laksana GS, Lane RH (2004) Uteroplacental insufficiency decreases small intestine growth and alters apoptotic homeostasis in term intrauterine growth retarded rats. Early Hum Dev 79:93–105. doi:10.1016/j.earlhumdev.2004.04.015
Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281:1322–1326
Zhang H, Li Y, Wang T (2015) Antioxidant capacity and concentration of redox-active trace mineral in fully weaned intra-uterine growth retardation piglets. J Anim Sci Biotechnol 6:48. doi:10.1186/s40104-015-0047-7
Wu G, Fang YZ, Yang S, Lupton JR, Turner ND (2004) Glutathione metabolism and its implications for health. J Nutr 134:489–492
Shan X, Aw TY, Jones DP (1990) Glutathione-dependent projection against oxidative injury. Pharmacol Ther 47:61–71
He Q, Ren P, Kong X, Xu W, Tang H, Yin Y, Wang Y (2011) Intrauterine growth restriction alters the metabonome of the serum and jejunum in piglets. Mol BioSyst 7:2147–2155. doi:10.1039/c1mb05024a
Alexandre-Gouabau M, Courant F, Le Gall G, Moyon T, Darmaun D, Parnet P, Coupé B, Antignac JP (2011) Offspring metabolomic response to maternal protein restriction in a rat model of intrauterine growth restriction (IUGR). J Proteome Res 10:3292–3302. doi:10.1021/pr2003193
MacLennan NK, James SJ, Melnyk S, Piroozi A, Jernigan S, Hsu JL, Janke SM, Pham TD, Lane RH (2004) Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats. Physiol Genomics 18:43–50. doi:10.1152/physiolgenomics.00042.2004
te Braake FW, Schierbeek H, Vermes A, Huijmans JG, van Goudoever JB (2009) High-dose cysteine administration does not increase synthesis of the antioxidant glutathione preterm infants. Pediatrics 124:e978–e984. doi:10.1542/peds.2008-2477
Anderson ME, Meister A (1987) Intracellular delivery of cysteine. Methods Enzymol 143:313–325
Levine RL, Mosoni L, Berlett BS, Stadtman ER (1996) Methionine residues as endogenous antioxidants in proteins. Proc Natl Acad Sci USA 93:15036–15040
Stipanuk MH (2004) Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. Annu Rev Nutr 24:539–577. doi:10.1146/annurev.nutr.24.012003.132418
Shen YB, Weaver AC, Kim SW (2014) Effect of feed grade l-methionine on growth performance and gut health in nursery pigs compared with conventional dl-methionine. J Anim Sci 92:5530–5539. doi:10.2527/jas.2014-7830
Hou Y, Wang L, Zhang W, Yang Z, Ding B, Zhu H, Liu Y, Qiu Y, Yin Y, Wu G (2012) Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide. Amino Acids 43:1233–1242. doi:10.1007/s00726-011-1191-9
Fang Z, Yao K, Zhang X, Zhao S, Sun Z, Tian G, Yu B, Lin Y, Zhu B, Jia G, Zhang K, Chen D, Wu D (2010) Nutrition and health relevant regulation of intestinal sulfur amino acid metabolism. Amino Acids 39:633–640. doi:10.1007/s00726-010-0502-x
Acknowledgements
This work was supported by the National Natural Science Foundation of China (Grant number 31572418) and the Phase II Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
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The use of animals for this research was approved by the Institutional Animal Care and Use Committee of Nanjing Agricultural University.
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Su, W., Zhang, H., Ying, Z. et al. Effects of dietary l-methionine supplementation on intestinal integrity and oxidative status in intrauterine growth-retarded weanling piglets. Eur J Nutr 57, 2735–2745 (2018). https://doi.org/10.1007/s00394-017-1539-3
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DOI: https://doi.org/10.1007/s00394-017-1539-3