Abstract
Sixty Duroc × Large White × Landrace pigs with an average initial body weight (BW) of 77.1 ± 1.3 kg were selected to investigate the effects of dietary supplementation with arginine (Arg) and/or glutamic acid (Glu) on free amino acid (FAA) profiles, expression of AA transporters, and growth-related genes in skeletal muscle. The animals were randomly assigned to one of five treatment groups (basic diet, iso-nitrogenous, Arg, Glu, and Arg + Glu groups). The results showed that plasma Glu concentration was lowest in the Arg + Glu group and highest in the Glu group (P < 0.05). In the longissimus dorsi (LD) muscle, the concentrations of histidine, Arg, and taurine in the Arg + Glu group were higher, and the concentrations of 3-methylhistidine was lower, than in the basic diet group (P < 0.05). The mRNA levels of ASC amino acid transporter-2 (ASCT2), L-type AA transporter 1, and sodium-coupled neutral amino acid transporter 2 in the LD muscle, as well as the mRNA levels of ASCT2 and proton-assisted amino acid transporter in the biceps femoris (BF) muscle, were higher in the Arg + Glu group compared to the basic diet group (P < 0.05). The mRNA levels of the muscle-specific RING finger-1 and muscle atrophy F-box genes in the LD muscle were downregulated in the Glu and Arg + Glu groups compared to the basic diet group (P < 0.05). Collectively, these findings suggest that dietary supplementation with both Arg and Glu increases intramuscular FAA concentrations and decreases the mRNA levels of genes involved in protein degradation in skeletal muscle.
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References
Baptista IL, Leal ML, Artioli GG, Aoki MS, Fiamoncini J, Turri AO, Curi R, Miyabara EH, Moriscot AS (2010) Leucine attenuates skeletal muscle wasting via inhibition of ubiquitin ligases. Muscle Nerve 41:800–808. https://doi.org/10.1002/mus.21578
Bodamer OA, Halliday D, Leonard JV (2000) The effects of l-alanine supplementation in late-onset glycogen storage disease type II. Neurology 55:710–712. https://doi.org/10.1212/WNL.55.5.710
Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294:1704–1708. https://doi.org/10.1126/science.1065874
Boutry C, Matsumoto H, Airinei G, Benamouzig R, Tome D, Blachier F, Bos C (2011) Monosodium glutamate raises antral distension and plasma amino acid after a standard meal in humans. Am J Physiol Gastrointest Liver Physiol 300:G137–G145. https://doi.org/10.1152/ajpgi.00299.2010
Broer S (2008) Amino acid transport across mammalian intestinal and renal epithelia. Physiol Rev 88(1):249–286. https://doi.org/10.1152/physrev.00018.2006
Dai Z, Wu Z, Hang S, Zhu W, Wu G (2015) Amino acid metabolism in intestinal bacteria and its potential implications for mammalian reproduction. Mol Hum Reprod 21:389–409. https://doi.org/10.1093/molehr/gav003
Davis TA, Fiorotto ML (2009) Regulation of muscle growth in neonates. Curr Opin Clin Nutr 12:78–85. https://doi.org/10.1097/mco.0b013e32831cef9f
Drummond MJ, Glynn EL, Fry CS, Timmerman KL, Volpi E, Rasmussen BB (2010) An increase in essential amino acid availability upregulates amino acid transporter expression in human skeletal muscle. Am J Physiol Endocrinol Metab 298:E1011–E1018. https://doi.org/10.1152/ajpendo.00690.2009
Duan YH, Li FN, Tan KR, Liu HN, Li YH, Liu YY, Kong XF, Tang YL, Wu GY, Yin YL (2015) Key mediators of intracellular amino acids signaling to mTORC1 activation. Amino Acids 47:857–867. https://doi.org/10.1007/s00726-015-1937-x
Duan Y, Duan Y, Li F, Li Y, Guo Q, Ji Y, Tan B, Li T, Yin Y (2016a) Effects of supplementation with branched-chain amino acids to low-protein diets on expression of genes related to lipid metabolism in skeletal muscle of growing pigs. Amino Acids 48:2131–2144. https://doi.org/10.1007/s00726-016-2223-2
Duan Y, Guo Q, Wen C, Wang W, Li Y, Tan B, Li F, Yin Y (2016b) Free amino acid profile and expression of genes implicated in protein metabolism in skeletal muscle of growing pigs fed low-protein diets supplemented with branched-chain amino acids. J Agric Food Chem 64:9390–9400. https://doi.org/10.1021/acs.jafc.6b03966
Duan Y, Li F, Li Y, Tang Y, Kong X, Feng Z, Anthony TG, Watford M, Hou Y, Wu G, Yin Y (2016c) The role of leucine and its metabolites in protein and energy metabolism. Amino Acids 48:41–51. https://doi.org/10.1007/s00726-015-2067-1
Guo P, Jiang ZY, Gao KG, Wang L, Yang XF, Hu YJ, Zhang J, Ma XY (2017) Low-level arginine supplementation (0.1%) of wheat-based diets in pregnancy increases the total and live-born litter sizes in gilts. Anim Prod Sci 57:1091–1096. https://doi.org/10.1071/AN15156
He QH, Kong XF, Wu GY, Ren PP, Tang HR, Hao FH, Huang RL, Li TJ, Tan B, Li P, Tang ZR, Yin YL, Wu YN (2009) Metabolomic analysis of the response of growing pigs to dietary l-arginine supplementation. Amino Acids 37:199–208. https://doi.org/10.1007/s00726-008-0192-9
He QH, Ren PP, Kong XF, Wu YN, Wu GY, Li P, Hao FH, Tang HR, Blachier F, Yin YL (2012) Comparison of serum metabolite compositions between obese and lean growing pigs using an NMR-based metabonomic approach. J Nutr Biochem 23:133–139. https://doi.org/10.1016/j.jnutbio.2010.11.007
Herningtyas EH, Okimura Y, Handayaningsih AE, Yamamoto D, Maki T, Iida K, Takahashi Y, Kaji H, Chihara K (2008) Branched-chain amino acids and arginine suppress MaFbx/atrogin-1 mRNA expression via mTOR pathway in C2C12 cell line. Biochem Biophys Acta 1780:1115–1120. https://doi.org/10.1016/j.bbagen.2008.06.004
Hisamatsu T, Okamoto S, Hashimoto M, Muramatsu T, Andou A, Uo M, Kitazume MT, Matsuoka K, Yajima T, Inoue N, Kanai T, Ogata H, Iwao Y, Yamakado M, Sakai R, Ono N, Ando T, Suzuki M, Hibi T (2012) Novel, objective, multivariate biomarkers composed of plasma amino acid profiles for the diagnosis and assessment of inflammatory bowel disease. PLoS One 7(1):e31131. https://doi.org/10.1371/journal.pone.0031131
Hu CJ, Jiang QY, Zhang T, Yin YL, Li FN, Deng JP, Wu GY, Kong XF (2017a) Dietary supplementation with arginine and glutamic acid modifies growth performance, carcass traits, and meat quality in growing-finishing pigs. J Anim Sci 95:2680–2689. https://doi.org/10.2527/jas.2017.1388
Hu CJ, Jiang QY, Zhang T, Yin YL, Li FN, Su JY, Wu GY, Kong XF (2017b) Dietary supplementation with arginine and glutamic acid enhances key lipogenic gene expression in growing pigs. J Anim Sci 95:5507–5515. https://doi.org/10.2527/jas2017.1703
Hundal HS, Taylor PM (2009) Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. Am J Physiol Endocrinol Metab 296:E603–E613. https://doi.org/10.1152/ajpendo.91002.2008
Ito T, Yoshikawa N, Ito H, Schaffer SW (2015) Impact of taurine depletion on glucose control and insulin secretion in mice. J Pharmacol Sci 129:59–64. https://doi.org/10.1016/j.jphs.2015.08.007
Jensen A, Figueiredo-Larsen M, Holm R, Broberg ML, Brodin B, Nielsen CU (2014) PAT1 (SLC36A1) shows nuclear localization and affects growth of smooth muscle cells from rats. Am J Physiol Endocrinol Metab 306:E65–E74. https://doi.org/10.1152/ajpendo.00322.2013
Kain V, Kapadia B, Viswakarma N, Seshadri S, Prajapati B, Jena PK, Teja Meda CL, Subramanian M, Kaimal Suraj S, Kumar ST, Prakash Babu P, Thimmapaya B, Reddy JK, Parsa KV, Misra P (2015) Co-activator binding protein PIMT mediates TNF-alpha induced insulin resistance in skeletal muscle via the transcriptional down-regulation of MEF2A and GLUT4. Sci Rep 5:15197. https://doi.org/10.1038/srep15197
Kang P, Wang X, Wu H, Zhu H, Hou Y, Wang L, Liu Y (2017) Glutamate alleviates muscle protein loss by modulating TLR4, NODs, Akt/FOXO and mTOR signaling pathways in LPS-challenged piglets. PLoS One 12:e0182246. https://doi.org/10.1371/journal.pone.0182246
Li F, Duan Y, Li Y, Tang Y, Geng M, Oladele OA, Kim SW, Yin Y (2015) Effects of dietary n-6:n-3 PUFA ratio on fatty acid composition, free amino acid profile and gene expression of transporters in finishing pigs. Br J Nutr 113:739–748. https://doi.org/10.1017/S0007114514004346
Li XG, Sui WG, Gao CQ, Yan HC, Yin YL, Li HC, Wang XQ (2016) L-Glutamate deficiency can trigger proliferation inhibition via down regulation of the mTOR/S6K1 pathway in pig intestinal epithelial cells. J Anim Sci 94:1541–1549. https://doi.org/10.2527/jas.2015-9432
Li YH, Li FN, Wu L, Liu YY, Wei HK, Li TJ, Tan BE, Kong XF, Wu F, Duan YH, Oladele OA, Yin YL (2017) Reduced dietary protein level influences the free amino acid and gene expression profiles of selected amino acid transceptors in skeletal muscle of growing pigs. J Anim Physiol Anim Nutr 101:96–104. https://doi.org/10.1111/jpn.12514
Liao SF, Wang T, Regmi N (2015) Lysine nutrition in swine and the related monogastric animals: muscle protein biosynthesis and beyond. SpringerPlus 4:147. https://doi.org/10.1186/s40064-015-0927-5
Liu ZQ, Jahn LA, Wei LP, Long W, Barrett EJ (2002) Amino acids stimulate translation initiation and protein synthesis through an Akt-independent pathway in human skeletal muscle. J Clin Endocrinol Metab 87:5553–5558. https://doi.org/10.1210/jc.2002-020424
Liu Y, Kong X, Li F, Tan B, Li Y, Duan Y, Yin Y, He J, Hu C, Blachier F, Wu GY (2016) Co-dependence of genotype and dietary protein intake to affect expression on amino acid/peptide transporters in porcine skeletal muscle. Amino Acids 48:75–90. https://doi.org/10.1007/s00726-015-2066-2
Merli M, Giusto M, Molfino A, Bonetto A, Rossi M, Ginanni Corradini S, Baccino FM, Rossi Fanelli F, Costelli P, Muscaritoli M (2013) MuRF-1 and p-GSK3beta expression in muscle atrophy of cirrhosis. Liver Int 33:714–721. https://doi.org/10.1111/liv.12128
Molkentin JD, Olson EN (1996) Combinatorial control of muscle development by basic helix-loop-helix and MADS-box transcription factors. Proc Natl Acad Sci 93:9366–9373. https://doi.org/10.1073/pnas.93.18.9366
Mundy HR, Williams JE, Cousins AJ, Lee PJ (2006) The effect of l-alanine therapy in a patient with adult onset glycogen storage disease type II. J Inherit Metab Dis 29:226–229. https://doi.org/10.1007/s10545-006-0238-7
Nardi F, Hoffmann TM, Stretton C, Cwiklinski E, Taylor PM, Hundal HS (2015) Proteasomal modulation of cellular SNAT2 (SLC38A2) abundance and function by unsaturated fatty acid availability. J Biol Chem 290:8173–8184. https://doi.org/10.1074/jbc.M114.625137
Nawashiro H, Otani N, Shinomiya N, Fukui S, Ooigawa H, Shima K, Matsuo H, Kanai Y, Endou H (2006) L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors. Int J Cancer 119:484–492. https://doi.org/10.1002/ijc.21866
Peng X, Hu L, Liu Y, Yan C, Fang ZF, Lin Y, Xu SY, Li J, Wu CM, Chen DW, Sun H, Wu D, Che LQ (2016) Effects of low-protein diets supplemented with indispensable amino acids on growth performance, intestinal morphology and immunological parameters in 13 to 35 kg pigs. Animal 10:1812–1820. https://doi.org/10.1017/S1751731116000999
Reidy PT, Walker DK, Dickinson JM, Gundermann DM, Drummond MJ, Timmerman KL, Cope MB, Mukherjea R, Jennings K, Volpi E, Rasmussen BB (2014) Soy-dairy protein blend and whey protein ingestion after resistance exercise increases amino acid transport and transporter expression in human skeletal muscle. J Appl Physiol 116:1353–1364. https://doi.org/10.1152/japplphysiol.01093.2013
Ren W, Yin J, Wu M, Liu G, Yang G, Xion Y, Su D, Wu L, Li T, Chen S, Duan J, Yin Y, Wu G (2014) Serum amino acids profile and the beneficial effects of l-arginine or l-glutamine supplementation in dextran sulfate sodium colitis. PLoS One 9:e88335. https://doi.org/10.1371/journal.pone.0088335
Rom O, Reznick AZ (2016) The role of E3 ubiquitin-ligases MuRF-1 and MAFbx in loss of skeletal muscle mass. Free Radic Biol Med 98:218–230. https://doi.org/10.1016/j.freeradbiomed.2015.12.031
Sales F, Pacheco D, Blair H, Kenyon P, McCoard S (2013) Muscle free amino acid profiles are related to differences in skeletal muscle growth between single and twin ovine fetuses near term. Springerplus 2:483. https://doi.org/10.1186/2193-1801-2-483
Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM (2008) The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320:1496–1501. https://doi.org/10.1126/science.1157535
Shi X, Garry DJ (2006) Muscle stem cells in development, regeneration, and disease. Genes Dev 20:1692–1708
Sugawara T, Ito Y, Nishizawa N, Suzuki H, Kobayashi H, Nagasawa T (2009) Measurement of the rate of myofibrillar protein degradation using the arteriovenous difference in plasma 3-methylhistidine concentration of rats. J Nutr Sci Vitaminol 55(4):381–384. https://doi.org/10.3177/jnsv.55.381
Suryawan A, Nguyen HV, Almonaci RD, Davis TA (2013) Abundance of amino acid transporters involved in mTORC1 activation in skeletal muscle of neonatal pigs is developmentally regulated. Amino Acids 45:523–530. https://doi.org/10.1007/s00726-012-1326-7
Tan B, Yin Y, Liu Z, Li X, Xu H, Kong X, Huang R, Tang W, Shinzato I, Smith SB, Wu G (2009) Dietary l-arginine supplementation increases muscle gain and reduces body fat mass in growing-finishing pigs. Amino Acids 37:169–175. https://doi.org/10.1007/s00726-008-0148-0
Tan B, Yin Y, Liu Z, Tang W, Xu H, Kong X, Li X, Yao K, Gu W, Smith SB, Wu G (2011) Dietary l-arginine supplementation differentially regulates expression of lipid-metabolic genes in porcine adipose tissue and skeletal muscle. J Nutr Biochem 22:441-445. https://doi.org/10.1016/j.jnutbio.2010.03.012
Taylor PM (2014) Role of amino acid transporters in amino acid sensing. Am J Clin Nutr 99:223s–230s. https://doi.org/10.3945/ajcn.113.070086
Vargas MA, Tirnauer JS, Glidden N, Kapiloff MS, Dodge-Kafka KL (2012) Myocyte enhancer factor 2 (MEF2) tethering to muscle selective A-kinase anchoring protein (mAKAP) is necessary for myogenic differentiation. Cell Signal 24:1496–1503. https://doi.org/10.1016/j.cellsig.2012.03.017
Walker DK, Drummond MJ, Dickinson JM, Borack MS, Jennings K, Volpi E, Rasmussen BB (2014) Insulin increases mRNA abundance of the amino acid transporter SLC7A5/LAT1 via an mTORC1-dependent mechanism in skeletal muscle cells. Physiol Rep 2:e00238. https://doi.org/10.1002/phy2.238
Wu GY (2010) Functional amino acids in growth, reproduction, and health. Adv Nutr 1:31–37. https://doi.org/10.3945/an.110.1008
Wu G (2018) Principles of animal nutrition. CRC Press, Boca Raton
Yin Y, Yao K, Liu Z, Gong M, Ruan Z, Deng D, Tan B, Liu Z, Wu G (2010) Supplementing l-leucine to a low-protein diet increases tissue protein synthesis in weanling pigs. Amino Acids 39:1477–1486. https://doi.org/10.1007/s00726-010-0612-5
Yin J, Ren WK, Duan JL, Wu L, Chen S, Li TJ, Yin YL, Wu GY (2014) Dietary arginine supplementation enhances intestinal expression of SLC7A7 and SLC7A1 and ameliorates growth depression in mycotoxin-challenged pigs. Amino Acids 46(4):883–892. https://doi.org/10.1007/s00726-013-1643-5
Acknowledgements
The present work was jointly supported by the National Natural Science Foundation of China (nos. 31572421 and 31772613) and National Basic Research Program of China (nos. 2013CB127305 and 2012CB124704).
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The protocol for this study was approved by the Committee on the Ethics of Animal Experiments of the Institute of Subtropical Agriculture, Chinese Academy of Sciences, and it was conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Institute of Subtropical Agriculture, Chinese Academy of Sciences.
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Hu, C.J., Li, F.N., Duan, Y.H. et al. Dietary supplementation with arginine and glutamic acid alters the expression of amino acid transporters in skeletal muscle of growing pigs. Amino Acids 51, 1081–1092 (2019). https://doi.org/10.1007/s00726-019-02748-9
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DOI: https://doi.org/10.1007/s00726-019-02748-9