L-citrulline supplementation enhances fetal growth and protein synthesis in rats with intrauterine growth restriction

Journal of Nutrition

Volumn 146, Issue 3, 2016, Pages 532-541

  Bourdon, Aurélie ^a   Parnet, Patricia ^a   Nowak, Christel ^a,b   Tran, Nhat Thang ^a   Winer, Norbert ^a,b   Darmaun, Dominique ^a,b  

^a Universite de Nantes   (France)

^b NANTES UNIVERSITY HOSPITAL   (France)

Author keywords

Amino acids; Developmental origins of health and disease; L arginine; Muscle; Nitric oxide; Obstetrics; Perinatal nutrition; Placenta; Protein metabolism; Stable isotopes

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE 2; ARGININE; CITRULLINE; CREATININE; DRINKING WATER; ENDOTHELIAL NITRIC OXIDE SYNTHASE; INDUCIBLE NITRIC OXIDE SYNTHASE; MESSENGER RNA; MUSCLE PROTEIN; NITRATE; NITRITE; ORNITHINE; TAP WATER; UREA; NITRIC OXIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CESAREAN SECTION; CONTROLLED STUDY; CREATININE URINE LEVEL; DIET SUPPLEMENTATION; FEMALE; FETUS; FETUS GROWTH; FETUS WEIGHT; GESTATIONAL AGE; INTRAUTERINE GROWTH RETARDATION; MALE; MASS FRAGMENTOGRAPHY; MATERNAL NUTRITION; NITROGEN BALANCE; NONHUMAN; NUTRITIONAL STATUS; PLACENTA DEVELOPMENT; PLACENTA WEIGHT; PROTEIN RESTRICTION; PROTEIN SYNTHESIS; RAT; TREATMENT RESPONSE; URINARY EXCRETION; URINE VOLUME; WEIGHT GAIN; ADVERSE EFFECTS; ANIMAL; DIETARY SUPPLEMENT; DRUG EFFECTS; FETAL GROWTH RETARDATION; FETUS DEVELOPMENT; METABOLISM; PLACENTA; PREGNANCY; SPRAGUE DAWLEY RAT;

ANIMALS; ARGININE; CITRULLINE; DIET, PROTEIN-RESTRICTED; DIETARY SUPPLEMENTS; FEMALE; FETAL DEVELOPMENT; FETAL GROWTH RETARDATION; FETAL WEIGHT; FETUS; MATERNAL NUTRITIONAL PHYSIOLOGICAL PHENOMENA; NITRIC OXIDE; NUTRITIONAL STATUS; PLACENTA; PREGNANCY; PROTEIN BIOSYNTHESIS; RATS; RATS, SPRAGUE-DAWLEY;

EID: 84960336081     PISSN: 00223166     EISSN: 15416100     Source Type: Journal    
DOI: 10.3945/jn.115.221267     Document Type: Article

References (87)

1. ACOG Practice bulletin no. 134: fetal growth restriction. Obstet Gynecol 2013;121:1122.
2. Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, Ezzati M, Grantham-McGregor S, Katz J, Martorell R, Uauy R. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 2013;382:427-51.
3. Wu G, Bazer FW, Wallace JM, Spencer TE. Board-invited review: intrauterine growth retardation: implications for the animal sciences. J Anim Sci 2006;84:2316-37.
4. Bernstein IM, Horbar JD, Badger GJ, Ohlsson A, Golan A. Morbidity and mortality among very-low-birth-weight neonates with intrauterine growth restriction. The Vermont Oxford Network. Am J Obstet Gynecol 2000;182(Pt 1):198-206.
5. Godfrey KM, Barker DJ. Fetal nutrition and adult disease. Am J Clin Nutr 2000;71(Suppl)1344S-52S.
6. Krause BJ, Hanson MA, Casanello P. Role of nitric oxide in placental vascular development and function. Placenta 2011;32:797-805.
7. Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J 2001;357:593-615.
8. Cynober L. Pharmacokinetics of arginine and related amino acids. J Nutr 2007;137(Suppl 2):1646S-9S.
9. Wu G, Bazer FW, Satterfield MC, Li X, Wang X, Johnson GA, Burghardt RC, Dai Z, Wang J, Wu Z. Impacts of arginine nutrition on embryonic and fetal development in mammals. Amino Acids 2013;45:241-56.
10. Gornik HL, Creager MA. Arginine and endothelial and vascular health. J Nutr 2004;134(Suppl):2880S-7S; discussion 95S.
11. de Pace V, Chiossi G, Facchinetti F. Clinical use of nitric oxide donors and L-arginine in obstetrics. J Matern Fetal Neonatal Med 2007;20:569-79.
12. Lassala A, Bazer FW, Cudd TA, Datta S, Keisler DH, Satterfield MC, Spencer TE, Wu G. Parenteral administration of L-arginine prevents fetal growth restriction in undernourished ewes. J Nutr 2010;140:1242-8.
13. Vosatka RJ, Hassoun PM, Harvey-Wilkes KB. Dietary L-arginine prevents fetal growth restriction in rats. Am J Obstet Gynecol 1998;178:242-6.
14. Mateo RD, Wu G, Bazer FW, Park JC, Shinzato I, Kim SW. Dietary L-arginine supplementation enhances the reproductive performance of gilts. J Nutr 2007;137:652-6.
15. Molnár M, Suto T, Toth T, Hertelendy F. Prolonged blockade of nitric oxide synthesis in gravid rats produces sustained hypertension, proteinuria, thrombocytopenia, and intrauterine growth retardation. Am J Obstet Gynecol 1994;170:1458-66.
16. Xiao XM, Li LP. L-Arginine treatment for asymmetric fetal growth restriction. Int J Gynaecol Obstet 2005;88:15-8.
17. Winer N, Branger B, Azria E, Tsatsaris V, Philippe HJ, Roze JC, Descamps P, Boog G, Cynober L, Darmaun D. L-Arginine treatment for severe vascular fetal intrauterine growth restriction: a randomized double-bind controlled trial. Clin Nutr 2009;28:243-8.
18. Windmueller HG, Spaeth AE. Source and fate of circulating citrulline. Am J Physiol 1981;241:E473-80.
19. Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Benazeth S, Cynober L. Almost all about citrulline in mammals. Amino Acids 2005;29:177-205.
20. Rouge C, Des Robert C, Robins A, Le Bacquer O, Volteau C, De La Cochetiere MF, Darmaun D. Manipulation of citrulline availability in humans. Am J Physiol Gastrointest Liver Physiol 2007;293:G1061-7.
21. Moinard C, Nicolis I, Neveux N, Darquy S, Benazeth S, Cynober L. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr 2008;99:855-62.
22. Lassala A, Bazer FW, Cudd TA, Li P, Li X, Satterfield MC, Spencer TE, Wu G. Intravenous administration of L-citrulline to pregnant ewes is more effective than L-arginine for increasing arginine availability in the fetus. J Nutr 2009;139:660-5.
23. Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev 2006;24:275-90.
24. Chien SJ, Lin KM, Kuo HC, Huang CF, Lin YJ, Huang LT, Tain YL. Two different approaches to restore renal nitric oxide and prevent hypertension in young spontaneously hypertensive rats: L-citrulline and nitrate. Transl Res 2014;163:43-52.
25. Osowska S, Moinard C, Neveux N, Loi C, Cynober L. Citrulline increases arginine pools and restores nitrogen balance after massive intestinal resection. Gut 2004;53:1781-6.
26. Osowska S, Duchemann T, Walrand S, Paillard A, Boirie Y, Cynober L, Moinard C. Citrulline modulates muscle protein metabolism in old malnourished rats. Am J Physiol Endocrinol Metab 2006;291:E582-6.
27. Jourdan M, Nair KS, Carter RE, Schimke J, Ford GC, Marc J, Aussel C, Cynober L. Citrulline stimulates muscle protein synthesis in the postabsorptive state in healthy people fed a low-protein diet-a pilot study. Clin Nutr 2015;34:449-56.
28. Schwenk WF, Berg PJ, Beaufrere B, Miles JM, Haymond MW. Use of t-butyldimethylsilylation in the gas chromatographic/mass spectrometric analysis of physiologic compounds found in plasma using electronimpact ionization. Anal Biochem 1984;141:101-9.
29. Bennet WM, O'Keefe SJ, Haymond MW. Comparison of precursor pools with leucine, alpha-ketoisocaproate, and phenylalanine tracers used to measure splanchnic protein synthesis in man. Metabolism 1993;42:691-5.
30. Marchini JS, Nguyen P, Deschamps JY, Maugere P, Krempf M, Darmaun D. Effect of intravenous glutamine on duodenal mucosa protein synthesis in healthy growing dogs. Am J Physiol 1999;276:E747-53.
31. Marconi AM, Paolini CL, Stramare L, Cetin I, Fennessey PV, Pardi G, Battaglia FC. Steady state maternal-fetal leucine enrichments in normal and intrauterine growth-restricted pregnancies. Pediatr Res 1999;46:114-9.
32. Paolini CL, Marconi AM, Ronzoni S, Di Noio M, Fennessey PV, Pardi G, Battaglia FC. Placental transport of leucine, phenylalanine, glycine, and proline in intrauterine growth-restricted pregnancies. J Clin Endocrinol Metab 2001;86:5427-32.
33. Murthi P, Fitzpatrick E, Borg AJ, Donath S, Brennecke SP, Kalionis B. GAPDH, 18S rRNA and YWHAZ are suitable endogenous reference genes for relative gene expression studies in placental tissues from human idiopathic fetal growth restriction. Placenta 2008;29:798-801.
34. Delamaire E, Parnet P, Coupe B, Hoebler C, Blat S, Poupeau G, Boquien CY, Champ M, Darmaun D. Long term metabolic impact of high protein neonatal feeding: a preliminary study in male rat pups born with a low birth weight. Clin Nutr 2012;31:741-8.
35. Coupe B, Grit I, Darmaun D, Parnet P. The timing of "catch-up growth" affects metabolism and appetite regulation in male rats born with intrauterine growth restriction. Am J Physiol Regul Integr Comp Physiol 2009;297:R813-24.
36. Bistrian BR. Recent advances in parenteral and enteral nutrition: a personal perspective. JPEN J Parenter Enteral Nutr 1990;14:329-34.
37. Kumar I, Land DG, Boyne AW. The determination of body composition of living animals. The daily endogenous creatinine excretion as a measure of body composition in rats. Br J Nutr 1959;13:320-9.
38. Davison JM, Noble MC. Serial changes in 24 hour creatinine clearance during normal menstrual cycles and the first trimester of pregnancy. Br J Obstet Gynaecol 1981;88:10-7.
39. Cornock R, Langley-Evans SC, Mobasheri A, McMullen S. The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins. Reprod Biol Endocrinol 2010;8:105.
40. Reynolds LP, Redmer DA. Angiogenesis in the placenta. Biol Reprod 2001;64:1033-40.
41. Suzuki T, Ikeda Y, Yoshikawa H, Tanaka K, Morita H, Yamamoto M, Takizawa T. Gestational changes in production of NO and expression of NOS mRNA isoforms in the rat placenta. J Vet Med Sci 2009;71:495-8.
42. Choi JW, Im MW, Pai SH. Nitric oxide production increases during normal pregnancy and decreases in preeclampsia. Ann Clin Lab Sci 2002;32:257-63.
43. Hefler LA, Reyes CA, O'Brien WE, Gregg AR. Perinatal development of endothelial nitric oxide synthase-deficient mice. Biol Reprod 2001;64:666-73.
44. Conrad KP, Joffe GM, Kruszyna H, Kruszyna R, Rochelle LG, Smith RP, Chavez JE, Mosher MD. Identification of increased nitric oxide biosynthesis during pregnancy in rats. FASEB J 1993;7:566-71.
45. Yallampalli C, Garfield RE. Inhibition of nitric oxide synthesis in rats during pregnancy produces signs similar to those of preeclampsia. Am J Obstet Gynecol 1993;169:1316-20.
46. Casanello P, Sobrevia L. Intrauterine growth retardation is associated with reduced activity and expression of the cationic amino acid transport systems y+/hCAT-1 and y+/hCAT-2B and lower activity of nitric oxide synthase in human umbilical vein endothelial cells. Circ Res 2002;91:127-34.
47. Hracsko Z, Hermesz E, Ferencz A, Orvos H, Novak Z, Pal A, Varga IS. Endothelial nitric oxide synthase is up-regulated in the umbilical cord in pregnancies complicated with intrauterine growth retardation. In Vivo 2009;23:727-32.
48. Lyall F, Greer IA, Young A, Myatt L. Nitric oxide concentrations are increased in the feto-placental circulation in intrauterine growth restriction. Placenta 1996;17:165-8.
49. Nasiell J, Nisell H, Blanck A, Lunell NO, Faxen M. Placental expression of endothelial constitutive nitric oxide synthase mRNA in pregnancy complicated by preeclampsia. Acta Obstet Gynecol Scand 1998;77:492-6.
50. Wu G, Flynn NE, Flynn SP, Jolly CA, Davis PK. Dietary protein or arginine deficiency impairs constitutive and inducible nitric oxide synthesis by young rats. J Nutr 1999;129:1347-54.
51. Wu G, Pond WG, Flynn SP, Ott TL, Bazer FW. Maternal dietary protein deficiency decreases nitric oxide synthase and ornithine decarboxylase activities in placenta and endometrium of pigs during early gestation. J Nutr 1998;128:2395-402.
52. Boger RH, Bode-Boger SM, Gerecke U, Gutzki FM, Tsikas D, Frolich JC. Urinary NO3-excretion as an indicator of nitric oxide formation in vivo during oral administration of L-arginine or L-name in rats. Clin Exp Pharmacol Physiol 1996;23:11-5.
53. Tsikas D. Analysis of nitrite and nitrate in biological fluids by assays based on the Griess reaction: appraisal of the Griess reaction in the L-arginine/nitric oxide area of research. J Chromatogr B Analyt Technol Biomed Life Sci 2007;851:51-70.
54. Luiking YC, Hallemeesch MM, van de Poll MC, Dejong CH, de Jonge WJ, Lamers WH, Deutz NE. Reduced citrulline availability by OTC deficiency in mice is related to reduced nitric oxide production. Am J Physiol Endocrinol Metab 2008;295:E1315-22.
55. Luiking YC, Poeze M, Ramsay G, Deutz NE. Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. Am J Clin Nutr 2009;89:142-52.
56. Morita M, Hayashi T, Ochiai M, Maeda M, Yamaguchi T, Ina K, Kuzuya M. Oral supplementation with a combination of L-citrulline and L-arginine rapidly increases plasma L-arginine concentration and enhances NO bioavailability. Biochem Biophys Res Commun 2014;454:53-7.
57. Hayashi T, Juliet PA, Matsui-Hirai H, Miyazaki A, Fukatsu A, Funami J, Iguchi A, Ignarro LJ. l-Citrulline and l-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits. Proc Natl Acad Sci U S A 2005;102:13681-6.
58. El-Kirsh AA, Abd El-Wahab HM, Abd-Ellah Sayed HF. The effect of L-arginine or L-citrulline supplementation on biochemical parameters and the vascular aortic wall in high-fat and high-cholesterol-fed rats. Cell Biochem Funct 2011;29:414-28.
59. Alexander BT, Llinas MT, Kruckeberg WC, Granger JP. L-arginine attenuates hypertension in pregnant rats with reduced uterine perfusion pressure. Hypertension 2004;43:832-6.
60. Michajlovskij N, Lichardus B, Kvetnansky R, Ponec J. Effect of acute and repeated immobilization stress on food and water intake, urine output and vasopressin changes in rats. Endocrinol Exp 1988;22:143-57.
61. Takizawa T, Yoshikawa H, Yamada M, Morita H. Expression of nitric oxide synthase isoforms and detection of nitric oxide in rat placenta. Am J Physiol Cell Physiol 2002;282:C762-7.
62. Ali M, Buhimschi I, Chwalisz K, Garfield RE. Changes in expression of the nitric oxide synthase isoforms in rat uterus and cervix during pregnancy and parturition. Mol Hum Reprod 1997;3:995-1003.
63. Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, Boger RH. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol 2008;65:51-9.
64. Thibault R, Flet L, Vavasseur F, Lemerle M, Ferchaud-Roucher V, Picot D, Darmaun D. Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over study. Clin Nutr 2011;30:807-11.
65. Fickling SA, Williams D, Vallance P, Nussey SS, Whitley GS. Plasma concentrations of endogenous inhibitor of nitric oxide synthesis in normal pregnancy and pre-eclampsia. Lancet 1993;342:242-3.
66. Holden DP, Fickling SA, Whitley GS, Nussey SS. Plasma concentrations of asymmetric dimethylarginine, a natural inhibitor of nitric oxide synthase, in normal pregnancy and preeclampsia. Am J Obstet Gynecol 1998;178:551-6.
67. Fowden AL, Forhead AJ, Coan PM, Burton GJ. The placenta and intrauterine programming. J Neuroendocrinol 2008;20:439-50.
68. Regnault TR, Friedman JE, Wilkening RB, Anthony RV, Hay WW Jr. Fetoplacental transport and utilization of amino acids in IUGR-a review. Placenta 2005;26(Suppl A):S52-62.
69. Jansson T, Powell TL. IFPA 2005 Award in Placentology Lecture. Human placental transport in altered fetal growth: does the placenta function as a nutrient sensor? A review. Placenta 2006;27(Suppl A): S91-7.
70. Cramer S, Beveridge M, Kilberg M, Novak D. Physiological importance of system A-mediated amino acid transport to rat fetal development. Am J Physiol Cell Physiol 2002;282:C153-60.
71. Rosario FJ, Jansson N, Kanai Y, Prasad PD, Powell TL, Jansson T. Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters. Endocrinology 2011;152:1119-29.
72. Timmerman M, Chung M, Wilkening RB, Fennessey PV, Battaglia FC, Meschia G. Relationship of fetal alanine uptake and placental alanine metabolism to maternal plasma alanine concentration. Am J Physiol 1998;275:E942-50.
73. Breuillard C, Cynober L, Moinard C. Citrulline and nitrogen homeostasis: an overview. Amino Acids 2015;47:685-91.
74. Le Plénier S, Walrand S, Noirt R, Cynober L, Moinard C. Effects of leucine and citrulline versus non-essential amino acids on muscle protein synthesis in fasted rat: a common activation pathway? Amino Acids 2012;43:1171-8.
75. Kong X, Tan B, Yin Y, Gao H, Li X, Jaeger LA, Bazer FW, Wu G. l-Arginine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells. JNutr Biochem 2012;23:1178-83.
76. Yao K, Yin YL, Chu W, Liu Z, Deng D, Li T, Huang R, Zhang J, Tan B, Wang W, Wu G. Dietary arginine supplementation increases mTOR signaling activity in skeletal muscle of neonatal pigs. J Nutr 2008;138:867-72.
77. Tsatsaris V, Fournier T, Winer N. [Pathophysiology of preeclampsia]. Ann Fr Anesth Reanim 2010;29:e13-8 (in French).
78. Ozaki T, Hawkins P, Nishina H, Steyn C, Poston L, Hanson MA. Effects of undernutrition in early pregnancy on systemic small artery function in late-gestation fetal sheep. Am J Obstet Gynecol 2000;183:1301-7.
79. Rutland CS, Latunde-Dada AO, Thorpe A, Plant R, Langley-Evans S, Leach L. Effect of gestational nutrition on vascular integrity in the murine placenta. Placenta 2007;28:734-42.
80. Itoh S, Brawley L, Wheeler T, Anthony FW, Poston L, Hanson MA. Vasodilation to vascular endothelial growth factor in the uterine artery of the pregnant rat is blunted by low dietary protein intake. Pediatr Res 2002;51:485-91.
81. Koumentaki A, Anthony F, Poston L, Wheeler T. Low-protein diet impairs vascular relaxation in virgin and pregnant rats. Clin Sci (Lond) 2002;102:553-60.
82. Jansson N, Pettersson J, Haafiz A, Ericsson A, Palmberg I, Tranberg M, Ganapathy V, Powell TL, Jansson T. Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol 2006;576(Pt 3):935-46.
83. Glazier JD, Cetin I, Perugino G, Ronzoni S, Grey AM, Mahendran D, Marconi AM, Pardi G, Sibley CP. Association between the activity of the system A amino acid transporter in the microvillous plasma membrane of the human placenta and severity of fetal compromise in intrauterine growth restriction. Pediatr Res 1997;42:514-9.
84. Wyrwoll CS, Seckl JR, Holmes MC. Altered placental function of 11beta-hydroxysteroid dehydrogenase 2 knockout mice. Endocrinology 2009;150:1287-93.
85. Langley-Evans SC, Phillips GJ, Benediktsson R, Gardner DS, Edwards CR, Jackson AA, Seckl JR. Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension in the rat. Placenta 1996;17:169-72.
86. Borzsonyi B, Demendi C, Pajor A, Rigo J, Jr., Marosi K, Agota A, Nagy ZB, Joo JG. Gene expression patterns of the 11beta-hydroxysteroid dehydrogenase 2 enzyme in human placenta from intrauterine growth restriction: the role of impaired feto-maternal glucocorticoid metabolism. Eur J Obstet Gynecol Reprod Biol 2016;161:12-7.
87. Tain YL, Hsieh CS, Lin IC, Chen CC, Sheen JM, Huang LT. Effects of maternal L-citrulline supplementation on renal function and blood pressure in offspring exposed to maternal caloric restriction: the impact of nitric oxide pathway. Nitric Oxide 2010;23:34-41.