Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
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$^1H$ NMR-Based Urinary Metabolic Profiling of Gender and Diurnal Variation in Healthy Korean Subjects

성별 및 채뇨 시각별 $^1H$ NMR 기반 뇨 대사체 프로파일링 연구

  • Jeong, Jin-Young (Institute of Aging, Hallym University) ;
  • Hwang, Geum-Sook (Korea Basic Science Institute, Seoul Center) ;
  • Park, Jong-Chul (Korea Basic Science Institute, Seoul Center) ;
  • Kim, Dong-Hyun (Department of Social and Preventive Medicine, College of Medicine, Hallym University) ;
  • Ha, Mi-Na (Department of Preventive Medicine, Dankook University College of Medicine)
  • 정진영 (한림대학교 고령사회연구소) ;
  • 황금숙 (한국기초과학지원연구원 서울센터) ;
  • 박종철 (한국기초과학지원연구원 서울센터) ;
  • 김동현 (한림대학교 의과대학 사회의학교실) ;
  • 하미나 (단국대학교 의과대학 예방의학교실)
  • Received : 2010.08.25
  • Accepted : 2010.12.10
  • Published : 2010.12.31
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Abstract

Objectives : This study was undertaken to examine the metabolomic changes due to gender and diurnal variation at sampling time and to identify an appropriate time point for urine sampling in epidemiologic studies using metabolomic profiles. Methods : Urine samples were collected twice a day (morning and afternoon) from 20 healthy Korean adults after fasting for 8 hours. The metabolomic assay was investigated using $^1H$ NMR spectroscopy coupled with the principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The metabolites responsible for differentiation between groups were identified through the loading plot of PLS-DA and quantified using Chenomx NMR Suite with a 600 MHz library. Results : Metabolites responsible for differentiation in gender and sampling time were creatinine, trimethyl anine oxide (TMAO), hippurate, mannitol, citrate and acetoacetate. Dimethylamine showed difference only as a factor of diurnal time. The level of creatinine was higher in men compared to women, and the levels of citrate, TMAO, hippurate, mannitol, and acetoacetate were higher in women compared to men. The levels of creatinine, TMAO, hippurate, dimethylamine and mannitol were higher in the morning rather than the afternoon while those of citrate and acetoacetate were higher in the afternoon rather than the morning. Conclusions : Since urinary metabolomic profiles varied by gender and diurnal cycle, urine sampling should be performed at the same time point for all participants in epidemiologic studies using metabolomic profiles.

Keywords

References

  1. Lenz EM, Bright J, Wilson ID, Morgan SR, Nash AF. A 1H NMR-based metabonomic study of urine and plasma samples obtained from healthy human subjects. J Pharm Biomed Anal 2003; 33(5): 1103-1115. https://doi.org/10.1016/S0731-7085(03)00410-2
  2. Keun HC. Metabonomic modeling of drug toxicity. Pharmacol Ther 2006; 109(1-2): 92-106. https://doi.org/10.1016/j.pharmthera.2005.06.008
  3. Lindon JC, Nicholson JK, Holmes E, Antti H, Bollard ME, Keun H, et al. Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project. Toxicol Appl Pharmacol 2003; 187(3): 137-146. https://doi.org/10.1016/S0041-008X(02)00079-0
  4. Laffel L. Ketone bodies: a Review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev 1999; 15(6): 412-426. https://doi.org/10.1002/(SICI)1520-7560(199911/12)15:6<412::AID-DMRR72>3.0.CO;2-8
  5. Kochhar S, Jacobs DM, Ramadan Z, Berruex F, Fuerholz A, Fay LB. Probing gender-specific metabolism differences in humans by nuclear magnetic resonance-based metabonomics. Anal Biochem 2006; 352(2): 274-281. https://doi.org/10.1016/j.ab.2006.02.033
  6. Slupsky CM, Rankin KN, Wagner J, Fu H, Chang D, Weljie AM, et al. Investigations of the effects of gender, diurnal variation, and age in human urinary metabolomic profiles. Anal Chem 2007; 79(18): 6995-7004. https://doi.org/10.1021/ac0708588
  7. Psihogios NG, Gazi IF, Elisaf MS, Seferiadis KI, Bairaktari ET. Gender-related and age-related urinalysis of healthy subjects by NMR-based metabonomics. NMR Biomed 2008; 21(3): 195-207. https://doi.org/10.1002/nbm.1176
  8. Mitchell SC, Zhang AQ, Smith RL. Dimethylamine and diet. Food Chem Toxicol 2008; 46(5): 1734-1738. https://doi.org/10.1016/j.fct.2008.01.010
  9. Solanky KS, Bailey NJ, Beckwith-Hall BM, Bingham S, Davis A, Holmes E, et al. Biofluid 1H NMR-based metabonomic techniques in nutrition research metabolic effects of dietary isoflavones in humans. J Nutr Biochem 2005; 16(4): 236-244. https://doi.org/10.1016/j.jnutbio.2004.12.005
  10. Lenz EM, Bright J, Wilson ID, Hughes A, Morrisson J, Lindberg H, et al. Metabonomics, dietary influences and cultural differences: a 1H NMR-based study of urine samples obtained from healthy British and Swedish subjects. J Pharm Biomed Anal 2004; 36(4): 841-849. https://doi.org/10.1016/j.jpba.2004.08.002
  11. Dumas ME, Maibaum EC, Teague C, Ueshima H, Zhou B, Lindon JC, Nicholson JK, et al. Assessment of analytical reproducibility of 1H NMR spectroscopy based metabonomics for large-scale epidemiological research: the INTERMAP Study. Anal Chem 2006; 78(7): 2199-2208. https://doi.org/10.1021/ac0517085
  12. Bollard ME, Holmes E, Lindon JC, Mitchell SC, Branstetter D, Zhang W, et al. Investigations into biochemical changes due to diurnal variation and estrus cycle in female rats using high-resolution 1H NMR spectroscopy of urine and pattern recognition. Anal Biochem 2001; 295(2): 194-202. https://doi.org/10.1006/abio.2001.5211
  13. Park IJ, Jeon HS, Kwak YS, Shin OH. Diurnal variation of urinary excretion of protein metabolites and electrolytes. Korean J Clin Pathol 1999; 19(4): 404-408. (Korean)
  14. Fan TW. Metabolite profiling by one- and two-dimensional NMR analysis of complex mixtures. Prog Nucl Magn Reson Spectrosc 1996; 28(2): 161-219. https://doi.org/10.1016/0079-6565(95)01017-3
  15. Eriksson L, Johansson E, Kettaneh-Wold N, Wold S. Introduction to multi and megavariate data analysis using projection methods (PCA & PLS). Umea: Umetrics: 1999: 43-64.
  16. Salek RM, Maguire ML, Bentley E, Rubtsov DV, Hough T, Cheeseman M, et al. A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human. Physiol Genomics 2006; 29(2): 99-108. https://doi.org/10.1152/physiolgenomics.00194.2006
  17. Holmes E, Nicholls AW, Lindon JC, Ramos S, Spraul M, Neidig P, et al. Development of a model for classification of toxin-induced lesions using 1H NMR spectroscopy of urine combined with pattern recognition. NMR Biomed 1998; 11(4-5): 235-244. https://doi.org/10.1002/(SICI)1099-1492(199806/08)11:4/5<235::AID-NBM507>3.0.CO;2-V
  18. Simpson DP. Citrate excretion: a window on renal metabolism. Am J Physiol 1983; 244(3): F223-F234.
  19. Guneral F, Bachmann C. Age-related reference values for urinary organic acids in a healthy Turkish pediatric population. Clin Chem 1994; 40(6): 862-866.
  20. Zuppi C, Messana I, Forni F, Rossi C, Pennacchietti L, Ferrari F, et al. 1H-NMR spectra of normal urines: reference ranges of the major metabolites. Clin Chim Acta 1997; 265(1): 85-97. https://doi.org/10.1016/S0009-8981(97)00110-1
  21. Dey J, Creighton A, Lindberg JS, Fuselier HA, Kok DJ, Cole FE, et al. Estrogen replacement increased the citrate and calcium excretion rates in postmenopausal women with recurrent urolithiasis. J Urol 2002; 167(1): 169-171. https://doi.org/10.1016/S0022-5347(05)65405-5
  22. D'Eon T, Braun B. The roles of estrogen and progesterone in regulating carbohydrate and fat utilization at rest and during exercise, J Womens Health Gend Based Med 2002; 11(3): 225-237. https://doi.org/10.1089/152460902753668439
  23. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev 2000; 80(3): 1107-1213.
  24. Sperlingova I, Dabrowska L, Stransky V, Kucera J, Tichy M. Human urine certified reference material CZ 6010: creatinine and toluene metabolites (hippuric acid and ocresol) and a benzene metabolite (phenol). Anal Bioanal Chem 2007; 387(7): 2419-2424. https://doi.org/10.1007/s00216-006-0708-7
  25. Delanghe J, De Slypere JP, De Buyzere M, Robbricht J, Wieme R, Vermeulen A. Normal reference values for creatine, creatinine, and carnitine are lower in vegetarians. Clin Chem 1989; 35(8): 1802-1803.
  26. Rehman HU. Fish odor syndrome. Postgrad Med J 1999; 75(886): 451-452. https://doi.org/10.1136/pgmj.75.886.451
  27. Yancey PH, Rhea MD, Kemp KM, Bailey DM. Trimethylamine oxide, betaine and other osmolytes in deep-sea animals: depth trends and effects on enzymes under hydrostatic pressure. Cell Mol Biol (Noisy-le-grand) 2004; 50(4); 371-376.
  28. Brewster D, Jones RS, Parke DV. The metabolism of shikimate in the rat. Biochem J 1978; 170(2): 257-264. https://doi.org/10.1042/bj1700257
  29. Nicholls AW, Mortishire-Smith RJ, Nicholson JK. NMR spectroscopic-based metabonomic studies of urinary metabolite variation in acclimatizing germ-free rats. Chem Res Toxicol 2003; 16(11): 1395-1404. https://doi.org/10.1021/tx0340293
  30. Williams RE, Eyton-Jones HW, Farnworth MJ, Gallagher R, Provan WM. Effect of intestinal microflora on the urinary metabolic profile of rats: a 1H-nuclear magnetic resonance spectroscopy study. Xenobiotica 2002; 32(9): 783-794. https://doi.org/10.1080/00498250210143047
  31. Phipps AN, Wright B, Stewart J, Wilson ID. Use of proton NMR for determining changes in metabolite excretion profiles induced by dietary changes in the rat. Pharm Sci 1997; 3(3): 143-146.
  32. Lundina TA, Knubovets TL, Sedov KR, Markova SA, Sibeldin LA. Variability of kidney tubular interstitial distortions in glomerulonephritis as measured by 1HNMR urinalysis. Clin Chim Acta 1993; 214(2): 165-173. https://doi.org/10.1016/0009-8981(93)90108-G
  33. Asatoor AM, Simenhoff ML. The origin of urinary dimethylamine. Biochim Biophys Acta 1965; 111(2): 384-392. https://doi.org/10.1016/0304-4165(65)90048-6
  34. Zhang AQ, Mitchell SC, Ayesh R, Smith RL. Dimethylamine formation in man. Biochem Pharmacol 1993; 45(11): 2185-2188. https://doi.org/10.1016/0006-2952(93)90187-2
  35. Mitchell SC, Zhang AQ, Noblet JM, Gillespie S, Jones N, Smith RL. Metabolic disposition of [14C]-trimethylamine N-oxide in rat: variation with dose and route of administration. Xenobiotica 1997; 27(11): 1187-1197. https://doi.org/10.1080/004982597239949
  36. Parry DM, Duerksen DR. Assessment of intestinal permeability with lactulose/mannitol: gum chewing is a potential confounding factor. Am J Gastroenterol 2001; 96(8): 2515-2516. https://doi.org/10.1111/j.1572-0241.2001.04075.x
  37. Wisselink HW, Weusthuis RA, Eggink G, Hugenholtz J, Grobben GJ. Mannitol production by lactic acid bacteria: a review. Int Dairy J 2002; 12(2-3): 151-161. https://doi.org/10.1016/S0958-6946(01)00153-4
  38. Francois B, Bachmann C, Schutgens BH. Glucose metabolism in a child with 3-hydroxy-3-methly-glutaryl-coenzyme A lyase deficiency. J Inherit Metab Dis 1981; 4(1): 163-164. https://doi.org/10.1007/BF02263641
  39. Nair KS, Welle SL, Halliday D, Campbell RG. Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans. J Clin Invest 1988; 82(1): 198-205. https://doi.org/10.1172/JCI113570