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Metabolomic analysis of the response of growing pigs to dietary l-arginine supplementation

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Abstract

Arginine plays an important role regulating nutrient metabolism, but the underlying mechanisms are largely unknown. This study was conducted to determine the effect of dietary arginine supplementation on the metabolome in serum of growing pigs using 1H nuclear magnetic resonance spectroscopy. Sixteen 120-day-old pigs (48 ± 1 kg) were randomly assigned to one of two groups, representing supplementation with 0 or 1.0% l-arginine to corn- and soybean meal-based diets. Serum was collected after a 46-day period of treatment. Dietary arginine supplementation decreased fat deposition and increased protein accretion in the body. Principal component analysis showed that serum concentrations of low density lipoprotein, very low density lipoprotein, and urea were lower, but concentrations of creatinine, tricarboxylic acid cycle metabolites, ornithine, lysine and tyrosine were greater in arginine-supplemented than in control pigs. Additionally, the arginine treatment affected serum concentrations of nitrogenous and lipid signaling molecules (glycerophosphorylcholine and myo-inositol) and intestinal bacterial metabolites (formate, ethanol, methylamine, dimethylamine, acetate, and propionate). These novel findings suggest that dietary arginine supplementation alters the catabolism of fat and amino acids in the whole body, enhances protein synthesis in skeletal muscle, and modulates intestinal microbial metabolism in growing pigs.

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Abbreviations

COSY:

Correlated spectroscopy

CPMG:

Carr–Purcell–Meiboom–Gill

GPC:

Glycerophosphorylcholine

LDL:

Low density lipoprotein

NMR:

Nuclear magnetic resonance

PCA:

Principal component analysis

TCA:

Tricarboxylic acid cycle

TMAO:

Trimethylamine-N-oxide

TOCSY:

Total correlation spectroscopy

VLDL:

Very low density lipoprotein

References

  • Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 101:15718–15723

    Article  PubMed  CAS  Google Scholar 

  • Bax A, Davis DG (1985) MLEV-17-based two-dimensional homonuclear magnetization transfer spectroscopy. J Magn Reson 65:355–360

    CAS  Google Scholar 

  • Bertram HC, Kristensen NB, Malmendal A, Nielsen NC, Bro R, Andersen HJ, Harmon DL (2005) A metabolomic investigation of splanchnic metabolism using 1H NMR spectroscopy of bovine blood plasma. Anal Chim Acta 536:1–6

    Article  CAS  Google Scholar 

  • Burt CT, Ribolow H (1994) Glycerol phosphorylcholine (GPC) and serine ethanolamine phosphodiester (SEP): evolutionary mirrored metabolites and their potential metabolic roles. Comp Biochem Physiol Biochem Mol Biol 108:11–20

    Article  PubMed  CAS  Google Scholar 

  • Chen LX, Yin YL, Jobgen WJS, Jobgen SC, Knabe DA, Hu WX, Wu GY (2007) In vitro oxidation of essential amino acids by jejunal mucosal cells of growing pigs. Livest Sci 109:19–23

    Article  Google Scholar 

  • Cornell HJ, Stelmasiak T (2007) A unified hypothesis of coeliac disease with implications for management of patients. Amino Acids 33:43–49

    Article  PubMed  CAS  Google Scholar 

  • Di Paolo G, De Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443:651–657

    Article  PubMed  CAS  Google Scholar 

  • Dumas ME, Maibaum EC, Teague C, Ueshima H, Zhou B, Lindon JC, Nicholson JK, Stamler J, Elliott P, Chan Q, Holmes E (2006) Assessment of analytical reproducibility of 1H NMR spectroscopy based metabonomics for large-scale epidemiological research: the INTERMAP Study. Anal Chem 78:2199–2208

    Article  PubMed  CAS  Google Scholar 

  • Fang ZF, Luo J, Qi ZL, Huang FR, Zhao SJ, Liu MY, Jiang SW, Peng J (2008) Effects of 2-hydroxy-4-methylthiobutyrate on portal plasma flow and net portal appearance of amino acids in piglets. Amino acids. doi: 10.1007/s00726-008-0110-1

  • Fu WJ, Haynes TE, Kohli R, Hu J, Shi W, Spencer TE, Carroll RJ, Meininger CJ, Wu G (2005) Dietary l-arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J Nutr 135:714–721

    PubMed  CAS  Google Scholar 

  • Galli F (2007) Amino acid and protein modification by oxygen and nitrogen species. Amino Acids 32:497–499

    Article  CAS  Google Scholar 

  • Grillo MA, Colombatto S (2007) S-Adenosylmethionine and radical-based catalysis. Amino Acids 32:197–202

    Article  PubMed  CAS  Google Scholar 

  • Han J, Liu YL, Fan W, Chao J, Hou YQ, Yin YL, Zhu HL, Meng GQ, Che ZQ (2008) Dietary l-arginine supplementation alleviates immunosuppression induced by cyclophosphamide in weaned pigs. Amino Acids. doi: 10.1007/s00726-008-0184-9

  • Hu CA, Khalil S, Zhaorigetu S, Liu Z, Tyler M, Wan G, Valle D (2008) Human ∆1-pyrroline-5-carboxylate synthase: function and regulation. Amino Acids 35:665–672

    Article  PubMed  CAS  Google Scholar 

  • Hurd RE (1990) Gradient-enhanced spectroscopy. J Magn Reson 87:422–428

    CAS  Google Scholar 

  • Jobgen WS, Fried SK, Fu WJ, Meininger CJ, Wu G (2006) Regulatory role for the arginine–nitric oxide pathway in metabolism of energy substrates. J Nutr Biochem 17:571–588

    Article  PubMed  CAS  Google Scholar 

  • Kim SW, Wu G (2004) Dietary arginine supplementation enhances the growth of milk-fed young pigs. J Nutr 134:625–630

    PubMed  CAS  Google Scholar 

  • Kim SW, Wu G (2008) Regulatory role for amino acids in mammary gland growth and milk synthesis. Amino Acids. doi: 10.1007/s00726-008-0151-5

  • Kong XF, Yin YL, He QH, Yin FG, Liu HJ, Li TJ, Huang RL, Geng MM, Ruan Z, Deng ZY, Xie MY, Wu G (2008) Dietary supplementation with Chinese herbal powder enhances ileal digestibilities and serum concentrations of amino acids in young pigs. Amino Acids. doi: 10.1007/s00726-008-0176-9

  • Lenz EM, Bright J, Wilson ID, Hughes A, Morrisson J, Lindberg H, Lockton A (2004) Metabonomics, dietary influences and cultural differences: a 1H NMR-based study of urine samples obtained from healthy British and Swedish subjects. J Pharm Biomed 36:841–849

    Article  CAS  Google Scholar 

  • Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444:1022–1023

    Article  PubMed  CAS  Google Scholar 

  • Li P, Yin YL, Li DF, Kim SW, Wu G (2007) Amino acids and immune function. Br J Nutr 98:237–252

    Article  PubMed  CAS  Google Scholar 

  • Li P, Mai K, Trushenski J, Wu G (2008) New developments in fish amino acid nutrition: towards functional and environmentally oriented aquafeeds. Amino Acids. doi: 10.1007/s00726-008-0171-1

  • Liao PQ, Wei L, Zhang XY, Li XJ, Wu HF, Wu YJ, Ni JZ, Pei FK (2007) Metabolic profiling of serum from gadolinium chloride-treated rats by 1H NMR spectroscopy. Anal Biochem 364:112–121

    Article  PubMed  CAS  Google Scholar 

  • Meiboom S, Gill D (1958) Modified spin-echo method for measuring nuclear relaxation times. Rev Sci Instrum 29:688–691

    Article  CAS  Google Scholar 

  • Montanez R, Rodriguez-Caso C, Sanchez-Jimenez F, Medina MA (2008) In silico analysis of arginine catabolism as a source of nitric oxide or polyamines in endothelial cells. Amino Acids 34:223–229

    Article  PubMed  CAS  Google Scholar 

  • National Research Council (1998) Nutrient requirements of swine, 10th edn. National Academic Press, Washington, DC

    Google Scholar 

  • Nicholson JK, Wilson ID (1989) High resolution proton magnetic resonance spectroscopy of biological fluids. Prog Nucl Magn Reson Spectrosc 21:449–501

    Article  CAS  Google Scholar 

  • Nicholson JK, Wilson ID (2003) Opinion: understanding ‘global’ systems biology: metabonomics and the continuum of metabolism. Nat Rev Drug Discov 2:668–676

    Article  PubMed  CAS  Google Scholar 

  • Nicholson JK, Foxall PJ, Spraul M, Farrant RD, Lindon JC (1995) 750 MHz 1H and 1H–13C NMR spectroscopy of human blood plasma. Anal Chem 67:793–811

    Article  PubMed  CAS  Google Scholar 

  • Nicholson JK, Holmes E, Lindon JC, Wilson ID (2004) The challenges of modeling mammalian biocomplexity. Nat Biotechnol 22:1268–1274

    Article  PubMed  CAS  Google Scholar 

  • Orlando GF, Wolf G, Engelmann M (2008) Role of neuronal nitric oxide synthase in the regulation of the neuroendocrine stress response in rodents: insights from mutant mice, Amino Acids 35:17–27

    Article  PubMed  CAS  Google Scholar 

  • Ou DY, Li DF, Cao YH, Li XL, Yin JD, Qiao SY, Wu G (2007) Dietary supplementation with zinc oxide decreases expression of the stem cell factor in the small intestine of weanling pigs. J Nutr Biochem 18:820–826

    Article  PubMed  CAS  Google Scholar 

  • Rezzi S, Ramadan Z, Fay LB, Kochhar S (2007a) Nutritional metabonomics: applications and perspectives. J Proteome Res 6:513–525

    Article  PubMed  CAS  Google Scholar 

  • Rezzi S, Ramadan Z, Martin FP, Fay LB, van Bladeren P, Lindon JC, Nicholson JK, Kochhar S (2007b) Human metabolic phenotypes link directly to specific dietary preferences in healthy individuals. J Proteome Res 6:4469–4477

    Article  PubMed  CAS  Google Scholar 

  • Satriano J (2007) Kidney growth, hypertrophy and the unifying mechanism of diabetic complications. Amino Acids 33:331–339

    Article  PubMed  CAS  Google Scholar 

  • Shantz LM, Levin VA (2007) Regulation of ornithine decarboxylase during oncogenic transformation: mechanisms and therapeutic potential. Amino Acids 33:213–223

    Article  PubMed  CAS  Google Scholar 

  • Siddiqui RA, Havey KA, Zaloga GP (2008) Modulation of enzymatic activities by n−3 polyunsaturated fatty acids to support cardiovascular health. J Nutr Biochem 19:417–437

    Article  PubMed  CAS  Google Scholar 

  • Suenaga R, Tomonaga S, Yamane H, Kurauchi I, Tsuneyoshi Y, Sato H, Denbow DM, Furuse M (2008) Intracerebroventricular injection of l-arginine induces sedative and hypnotic effects under an acute stress in neonatal chicks. Amino Acids 35:139–146

    Article  PubMed  CAS  Google Scholar 

  • Sugita Y, Takao K, Toyama Y, Shirahata A (2007) Enhancement of intestinal absorption of macromolecules by spermine in rats. Amino Acids 33:253–260

    Article  PubMed  CAS  Google Scholar 

  • Suryawan A, O’Connor PMJ, Bush JA, Nguyen HV, Davis TA (2008) Differential regulation of protein synthesis by amino acids and insulin in peripheral and visceral tissues of neonatal pigs. Amino Acids. doi: 10.1007/s00726-008-0149-z

  • Tan B, Li XG, Kong X, Huang R, Ruan Z, Yao K, Deng Z, Xie M, Shinzato I, Yin Y, Wu G (2008a) Dietary l-arginine supplementation enhances the immune status in early-weaned piglets. Amino Acids. doi: 10.1007/s00726-008-0155-1

  • Tan B, Yin Y, Liu Z, Li X, Xu H, Kong X, Huang R, Tang W, Shinzato I, Smith SB, Wu G (2008b) Dietary l-arginine supplementation increases muscle gain and reduces body fat mass in growing–finishing pigs. Amino Acids. doi: 10.1007/s00726-008-0148-0

  • Tannock GW (2004) A special fondness for lactobacilli. Appl Environ Microbiol 70:3189–3194

    Article  PubMed  CAS  Google Scholar 

  • Tokumura A (2004) Metabolic pathways and physiological and pathological significances of lysolipid phosphate mediators. J Cell Biochem 92:869–881

    Article  PubMed  CAS  Google Scholar 

  • Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031

    Article  PubMed  Google Scholar 

  • Van Dorsten FA, Daykin CA, Mulder TP, Van Duynhoven JP (2006) Metabonomics approach to determine metabolic differences between green tea and black tea consumption. J Agric Food Chem 54:6929–6938

    Article  PubMed  CAS  Google Scholar 

  • Van Goudoever JB, Stoll B, Henry JF, Burrin DG, Reeds PJ (2000) Adaptive regulation of intestinal lysine metabolism. Proc Natl Acad Sci USA 97:11620–11625

    Article  PubMed  Google Scholar 

  • Wang Y, Lawler D, Larson B, Ramadan Z, Kochhar S, Holmes E, Nicholson JK (2007) Metabonomic investigations of aging and caloric restriction in a life-long dog study. J Proteome Res 6:1846–1854

    Article  PubMed  CAS  Google Scholar 

  • Wang WW, Qiao SY, Li DF (2008a) Amino acids and gut function. Amino Acids. doi: 10.1007/s00726-008-0152-4

  • Wang JJ, Wu G, Zhou HJ, Wang FL (2008b) Emerging technologies for amino acid nutrition research in the post-genome era. Amino Acids. doi:10.1007/s00726-008-0193-8

  • Wu G, Meininger CJ (2002) Regulation of nitric oxide synthesis by dietary factors. Annu Rev Nutr 22:61–86

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Morris SMJ (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17

    PubMed  CAS  Google Scholar 

  • Wu GY, Gunasekara A, Brunengraber H, Marliss EB (1991) Effects of extracellular pH, CO2, and HCO3 − on ketogenesis in perfused rat liver. Am J Physiol Endocrinol Metab 261:E221–E226

    CAS  Google Scholar 

  • Wu DH, Chen AD, Johnson CS (1995) An improved diffusion-ordered spectroscopy experiment incorporating bipolar-gradient pulses. J Magn Reson Ser A 115:260–264

    Article  CAS  Google Scholar 

  • Wu G, Bazer FW, Cudd TA, Jobgen WS, Kim SW, Lassala A, Li P, Matis JH, Meininger CJ, Spencer TE (2007a) Pharmacokinetics and safety of arginine supplementation in animals. J Nutr 137:1673S–1680S

    PubMed  CAS  Google Scholar 

  • Wu GY, Bazer FW, Davis TA, Jaeger LA, Johnson GA, Kim SW, Knabe DA, Meininger CJ, Spencer TE, Yin YL (2007b) Important roles for the arginine family of amino acids in swine nutrition and production. Livest Sci 112:8–22

    Article  Google Scholar 

  • Wu G, Collins JK, Perkins-Veazie P, Siddiq M, Dolan KD, Kelly KA, Heaps CL, Meininger CJ (2007c) Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. J Nutr 137:2680–2685

    PubMed  CAS  Google Scholar 

  • Wu G, Bazer FW, Datta S, Johnson GA, Li P, Satterfield MC, Spencer TE (2008) Proline metabolism in the conceptus: implications for fetal growth and development. Amino Acids 35:691–702

    Article  PubMed  CAS  Google Scholar 

  • Yang Y, Li C, Nie X, Feng X, Chen W, Yue Y, Tang H, Deng F (2007) Metabonomic studies of human hepatocellular carcinoma using high-resolution magic-angle spinning 1H NMR spectroscopy in conjunction with multivariate data analysis. J Proteome Res 6:2605–2614

    Article  PubMed  CAS  Google Scholar 

  • Yao K, Yin YL, Chu W, Liu Z, Deng D, Li T, Huang R, Zhang J, Tan B, Wang W, Wu G (2008) Dietary arginine supplementation increases mTOR signaling activity in skeletal muscle of neonatal pigs. J Nutr 138:867–872

    PubMed  CAS  Google Scholar 

  • Yen JT, Nienaber JA, Pond WG, Varel VH (1985) Effect of carbadox on growth, fasting metabolism, thyroid function and gastrointestinal tract in young pigs. J Nutr 115:970–979

    PubMed  CAS  Google Scholar 

  • Yin YL, Deng ZY, Huang HL, Li TJ, Zhong HY (2004) The effect of arabinoxylanase and protease supplementation on nutritional value of diets containing wheat bran or rice bran in growing pig. J Anim Feed Sci 13:445–461

    Google Scholar 

  • Yin FG, Liu YL, Yin YL, Kong XF, Huang RL, Li TJ, Wu GY, Hou Y (2008) Dietary supplementation with Astragalus polysaccharide enhances ileal digestibilities and serum concentrations of amino acids in early weaned piglets. Amino Acids. doi: 10.1007/s00726-008-0142-6

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Acknowledgments

We thank Dr. Darrell Knabe and Dr. Junjun Wang for helpful comments on the manuscript. This research was jointly supported by grants from the Chinese Academy of Sciences and Knowledge Innovation Project (KSCX2-YW-N-051, KZCX3-SW-441, YW-N-022, and KSCX2-SW323), K·C. Wong Education Foundation (Hong Kong), National Basic Research Program of China (2004CB117502), NSFC (30528006, 30671517, 30700581, 30771558 and 30371038), the Outstanding Overseas Chinese Scholars Fund of the Chinese Academy of Sciences (2005-1-4 and 2005-1-7), Fund of Agricultural Science and Technology outcome application (2006GB24910468), National Scientific and Technological Support Project (2006BAD12B07 and 2006BAD12B02-5-2), Guang Dong Province and Guangzhou City Project (2006B200330005), Program for Gangjiang Scholars and Innovative University Research Team (65292 and IRT0540), Hunan Key Projects 2007FJ1003,06FJ3046), Texas AgriLife Research (H-8200), and National Research Initiative Competitive Grant (2008-35206-18764) from the USDA Cooperative State Research, Education, and Extension Service.

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Authors and Affiliations

  1. State Key Laboratory of Food Science and Technology, Nanchang University, 330047, Nanchang, Jiangxi, China

    Qinghua He, Xiangfeng Kong & Yulong Yin

  2. Laboratory of Animal Nutritional Physiology and Metabolism, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, 410125, Changsha, Hunan, China

    Qinghua He, Xiangfeng Kong, Guoyao Wu, Ruilin Huang, Tiejun Li, Bie Tan, Peng Li, Zhiru Tang & Yulong Yin

  3. National Institute for Nutrition and Food Safety, Chinese CDC, 100050, Beijing, China

    Qinghua He & Yongning Wu

  4. Department of Animal Science, Texas A&M University, College Station, TX, 77843-2471, USA

    Guoyao Wu & Peng Li

  5. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, The Chinese Academy of Sciences, 430071, Wuhan, Hubei, China

    Pingping Ren, Huiru Tang & Fuhua Hao

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  1. Qinghua He
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  2. Xiangfeng Kong
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  13. Yongning Wu
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Correspondence to Yulong Yin or Yongning Wu.

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He, Q., Kong, X., Wu, G. et al. Metabolomic analysis of the response of growing pigs to dietary l-arginine supplementation. Amino Acids 37, 199–208 (2009). https://doi.org/10.1007/s00726-008-0192-9

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