Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline

FASEB Journal

Volumn 24, Issue 8, 2010, Pages 2962-2975

  Sha, Wei ^a   Da Costa, Kerry Ann ^d   Fischer, Leslie M ^d   Milburn, Michael V ^e   Lawton, Kay A ^e   Berger, Alvin ^e,f   Jia, Wei ^b   Zeisel, Steven H ^c,d  

^a UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE   (United States)

^b UNIVERSITY OF NORTH CAROLINA AT GREENSBORO   (United States)

^c UNIVERSITY OF NORTH CAROLINA   (United States)

^d University of North Carolina   (United States)

^e METABOLON INC   (United States)

^f CARGILL INC   (United States)

Author keywords

Fatty liver; Metabolomics; PEMT; Plasma

Indexed keywords

CHOLINE; CYANOCOBALAMIN; FOLIC ACID; METHIONINE; MINERAL; MULTIVITAMIN; PYRIDOXINE;

ADULT; AGED; ARTICLE; BLOOD SAMPLING; BODY MASS; CHEMICAL ANALYSIS; CLINICAL ASSESSMENT; CONTROLLED STUDY; DIET THERAPY; DIETARY INTAKE; FATTY LIVER; FEEDING; FEMALE; FOOD INTAKE; HUMAN; LIVER; LIVER DYSFUNCTION; LIVER METABOLISM; MAJOR CLINICAL STUDY; MALE; METABOLOMICS; MOLECULE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; RISK FACTOR; VITAMIN SUPPLEMENTATION;

CHOLINE; CHOLINE DEFICIENCY; DIET; FATS; HUMANS; LIVER; LIVER DISEASES; METABOLOMICS; PREDICTIVE VALUE OF TESTS;

EID: 77955807773     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.09-154054     Document Type: Article

References (75)

1. Zeisel, S. H. (2006) Choline: critical role during fetal development and dietary requirements in adults. Annu. Rev. Nutr. 26, 229-250
2. Niculescu, M. D., and Zeisel, S. H. (2002) Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. J. Nutr. 132, 2333S-2335S
3. Finkelstein, J. D. (2000) Pathways and regulation of homocysteine metabolism in mammals. Semin. Thromb. Hemost. 26, 219-225
4. Kim, Y. I., Miller, J. W., da Costa, K. A., Nadeau, M., Smith, D., Selhub, J., Zeisel, S. H., and Mason, J. B. (1995) Folate deficiency causes secondary depletion of choline and phosphocholine in liver. J. Nutr. 124, 2197-2203
5. Selhub, J., Seyoum, E., Pomfret, E. A., and Zeisel, S. H. (1991) Effects of choline deficiency and methotrexate treatment upon liver folate content and distribution. Cancer Res. 51, 16-21
6. Varela-Moreiras, G., Selhub, J., da Costa, K., and Zeisel, S. H. (1992) Effect of chronic choline deficiency in rats on liver folate content and distribution. J. Nutr. Biochem. 3, 519-522
7. Blusztajn, J. K., Zeisel, S. H., and Wurtman, R. J. (1985) Developmental changes in the activity of phosphatidylethanolamine N-methyltransferases in rat brain. Biochem. J. 232, 505-511
8. Institute of Medicine and National Academy of Sciences USA. (1998) Choline. In Dietary Reference Intakes for Folate, Thiamin, Riboflavin, Niacin, Vitamin B12, Panthothenic Acid, Biotin, and Choline, Vol. 1, pp. 390-422, National Academy Press, Washington, DC
9. Busby, M. G., Fischer, L., Da Costa, K. A., Thompson, D., Mar, M. H., and Zeisel, S. H. (2004) Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria. J. Am. Diet. Assoc. 104, 1836-1845
10. Da Costa, K. A., Badea, M., Fischer, L. M., and Zeisel, S. H. (2004) Elevated serum creatine phosphokinase in choline-deficient humans: mechanistic studies in C2C12 mouse myoblasts. Am. J. Clin. Nutr. 80, 163-170
11. Da Costa, K. A., Gaffney, C. E., Fischer, L. M., and Zeisel, S. H. (2005) Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load. Am. J. Clin. Nutr. 81, 440-444
12. Fischer, L. M., daCosta, K., Kwock, L., Stewart, P., Lu, T. S., Stabler, S., Allen, R., and Zeisel, S. (2007) Sex and menopausal status influence human dietary requirements for the nutrient choline. Am. J. Clin. Nutr. 85, 1275-1285
13. Yao, Z. M., and Vance, D. E. (1988) The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. J. Biol. Chem. 263, 2998-3004
14. Albright, C. D., Salganik, R. I., Kaufmann, W. K., Vrablic, A. S., and Zeisel, S. H. (1998) A p53-dependent G1 checkpoint function is not required for induction of apoptosis by acute choline deficiency in immortalized rat hepatocytes in culture. J. Nutr. Biochem. 9, 476-481
15. Da Costa, K. A., Niculescu, M. D., Craciunescu, C. N., Fischer, L. M., and Zeisel, S. H. (2006) Choline deficiency increases lymphocyte apoptosis and DNA damage in humans. Am. J. Clin. Nutr. 84, 88-94
16. Resseguie, M., Song, J., Niculescu, M. D., da Costa, K. A., Randall, T. A., and Zeisel, S. H. (2007) Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes. FASEB J. 21, 2622-2632
17. Da Costa, K. A., Kozyreva, O. G., Song, J., Galanko, J. A., Fischer, L. M., and Zeisel, S. H. (2006) Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J. 20, 1336-1344
18. Kohlmeier, M., da Costa, K. A., Fischer, L. M., and Zeisel, S. H. (2005) Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans. Proc. Natl. Acad. Sci. U. S. A. 102, 16025-16030
19. Savendahl, L., Mar, M. H., Underwood, L., and Zeisel, S. (1997) Prolonged fasting results in diminished plasma choline concentration but does not cause liver dysfunction. Am. J. Clin. Nutr. 66, 622-625
20. Zeisel, S. H., da Costa, K. A., Franklin, P. D., Alexander, E. A., Lamont, J. T., Sheard, N. F., and Beiser, A. (1991) Choline, an essential nutrient for humans. FASEB J. 5, 2093-2098
21. Jensen, H. H., Batres-Marquez, S. P., Carriquiry, A., and Schalinske, K. L. (2007) Choline in the diets of the U.S. population: NHANES, 2003-2004. FASEB J. 21, lb219
22. Cho, E., Zeisel, S. H., Jacques, P., Selhub, J., Dougherty, L., Colditz, G. A., and Willett, W. C. (2006) Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am. J. Clin. Nutr. 83, 905-911
23. Shaw, G. M., Carmichael, S. L., Laurent, C., and Rasmussen, S. A. (2006) Maternal nutrient intakes and risk of orofacial clefts. Epidemiology. 17, 285-291
24. Shaw, G. M., Carmichael, S. L., Yang, W., Selvin, S., and Schaffer, D. M. (2004) Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am. J. Epidemiol. 160, 102-109
25. Xu, X., Gammon, M. D., Zeisel, S. H., Bradshaw, P. T., Wetmur, J. G., Teitelbaum, S. L., Neugut, A. I., Santella, R. M., and Chen, J. (2009) High intakes of choline and betaine reduce breast cancer mortality in a population-based study. FASEB J. 23, 4022-4028
26. Buchman, A., Dubin, M., Moukarzel, A., Jenden, D., Roch, M., Rice, K., Gornbein, J., and Ament, M. (1995) Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology 22, 1399-1403
27. Buchman, A. L., Ament, M. E., Sohel, M., Dubin, M., Jenden, D. J., Roch, M., Pownall, H., Farley, W., Awal, M., and Ahn, C. (2001) Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial. J. Parenter. Enteral. Nutr. 25, 260-268
28. Sheard, N. F., Tayek, J. A., Bistrian, B. R., Blackburn, G. L., and Zeisel, S. H. (1986) Plasma choline concentration in humans fed parenterally. Am. J. Clin. Nutr. 43, 219-224
29. Nehra, V., Angulo, P., Buchman, A. L., and Lindor, K. D. (2001) Nutritional and metabolic considerations in the etiology of nonalcoholic steatohepatitis. Digest. Dis. Sci. 46, 2347-2352
30. Song, J., da Costa, K. A., Fischer, L. M., Kohlmeier, M., Kwock, L., Wang, S., and Zeisel, S. H. (2005) Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD). FASEB J. 19, 1266-1271
31. Dong, H., Wang, J., Li, C., Hirose, A., Nozaki, Y., Takahashi, M., Ono, M., Akisawa, N., Iwasaki, S., Saibara, T., and Onishi, S. (2007) The phosphatidylethanolamine N-methyltransferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population. J. Hepatol. 46, 915-920
32. Jun, D. W., Han, J. H., Jang, E. C., Kim, S. H., Jo, Y. J., Park, Y. S., and Chae, J. D. (2009) Polymorphisms of microsomal triglyceride transfer protein gene and phosphatidylethanolamine N-methyltransferase gene in alcoholic and nonalcoholic fatty liver disease in Koreans. Eur. J. Gastroenterol. Hepatol. 21, 667-672
33. Romeo, S., Cohen, J. C., and Hobbs, H. H. (2006) No association between polymorphism in PEMT (V175M) and hepatic triglyceride content in the Dallas Heart Study. FASEB J. 20, 2180; author reply 2181-2182
34. Zeisel, S. (2006) People with fatty liver are more likely to have the PEMT rs7946 SNP, yet populations with the mutant allele do not have fatty liver. FASEB J. 20, 2181-2182
35. Da Costa, K., Cochary, E. F., Blusztajn, J. K., Garner, S. C., and Zeisel, S. H. (1993) Accumulation of 1,2-sn-diradylglycerol with increased membrane-associated protein kinase C may be the mechanism for spontaneous hepatocarcinogenesis in choline-deficient rats. J. Biol. Chem. 268, 2100-2105
36. Zeisel, S. H. (2007) Nutrigenomics and metabolomics will change clinical nutrition and public health practice: insights from studies on dietary requirements for choline. Am. J. Clin. Nutr. 86, 542-548
37. Keun, H. C., and Athersuch, T. J. (2007) Application of metabonomics in drug development. Pharmacogenomics 8, 731-741
38. Jacobs, A. (2009) An FDA perspective on the nonclinical use of the X-Omics technologies and the safety of new drugs. Toxicol. Lett. 186, 32-35
39. Rubino, F. M., Pitton, M., Di Fabio, D., and Colombi, A. (2009) Toward an "omic" physiopathology of reactive chemicals: thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds. Mass. Spectrom. Rev. 28, 725-784
40. Beger, R. D., Sun, J., and Schnackenberg, L. K. (2009) Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity. Toxicol Appl Pharmacol 243, 154-166
41. Sreekumar, A., Poisson, L. M., Rajendiran, T. M., Khan, A. P., Cao, Q., Yu, J., Laxman, B., Mehra, R., Lonigro, R. J., Li, Y., Nyati, M. K., Ahsan, A., Kalyana-Sundaram, S., Han, B., Cao, X., Byun, J., Omenn, G. S., Ghosh, D., Pennathur, S., Alexander, D. C., Berger, A., Shuster, J. R., Wei, J. T., Varambally, S., Beecher, C., and Chinnaiyan, A. M. (2009) Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 457, 910-914
42. Koc, H., Mar, M. H., Ranasinghe, A., Swenberg, J. A., and Zeisel, S. H. (2002) Quantitation of choline and its metabolites in tissues and foods by liquid chromatography/electrospray ionization-isotope dilution mass spectrometry. Anal. Chem. 74, 4734-4740
43. Fishbein, M., Gardner, K., Potter, C., Schmalbrock, P., and Smith, M. (1997) Introduction of fast MR imaging in the assessment of hepatic steatosis. Magn. Reson. Imaging 15, 287-293
44. Saadeh, S., Younossi, Z. M., Remer, E. M., Gramlich, T., Ong, J. P., Hurley, M., Mullen, K. D., Cooper, J. N., and Sheridan, M. J. (2002) The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 123, 745-750
45. Ma, X., Holalkere, N. S., Kambadakone, R. A., Mino-Kenudson, M., Hahn, P. F., and Sahani, D. V. (2009) Imaging-based quantification of hepatic fat: methods and clinical applications. Radiographics 29, 1253-1277
46. Boudonck, K. J., Mitchell, M. W., Nemet, L., Keresztes, L., Nyska, A., Shinar, D., and Rosenstock, M. (2009) Discovery of metabolomics biomarkers for early detection of nephrotoxicity. Toxicol. Pathol. 37, 280-292
47. Lawton, K. A., Berger, A., Mitchell, M., Milgram, K. E., Evans, A. M., Guo, L., Hanson, R. W., Kalhan, S. C., Ryals, J. A., and Milburn, M. V. (2008) Analysis of the adult human plasma metabolome. Pharmacogenomics 9, 383-397
48. Evans, A. M., DeHaven, C. D., Barrett, T., Mitchell, M., and Milgram, M. (2009) Integrated, nontargeted ultrahigh performance liquid chromatography/ elctrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems. Anal. Chem. 81, 6656-6667
49. Barrett, T., Dehaven, C. D., and Alexander, D. C. (2008) System, method, and computer program product using a database in a computing system to compile and compare metabolomic data obtained from a plurality of samples. U.S. Patent 7,433,787; issued October 27, 2008. U.S. Patent and Trademark Office, Washington, DC
50. Storey, J. D., and Tibshirani, R. (2003) Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. U. S. A. 100, 9440-9445
51. Yeung, K. Y., and Bumgarner, R. E. (2003) Multiclass classification of microarray data with repeated measurements: application to cancer. Genome Biol. 4, R83
52. Atkinson, W., Downer, P., Lever, M., Chambers, S. T., and George, P. M. (2007) Effects of orange juice and proline betaine on glycine betaine and homocysteine in healthy male subjects. Eur. J. Nutr. 46, 446-452
53. Cui, Z., and Vance, D. E. (1996) Expression of phosphatidylethanolamine N-methyltransferase-2 is markedly enhanced in long term choline-deficient rats. J. Biol. Chem. 271, 2839-2843
54. Zeisel, S. H., Zola, T., daCosta, K., and Pomfret, E. A. (1989) Effect of choline deficiency on S-adenosylmethionine and methionine concentrations in rat liver. Biochem. J. 259, 725-729
55. Michael, U. F., Cookson, S. L., Chavez, R., and Pardo, V. (1975) Renal function in the choline-deficient rat. Proc. Soc. Exp. Biol. Med. 150, 672-676
56. Horio, M., Yamauchi, A., Moriyama, T., Imai, E., and Orita, Y. (1997) Osmotic regulation of amino acids and system A transport in Madin-Darby canine kidney cells. Am. J. Physiol. Cell. Physiol. 272, C804-C809
57. Kempson, S. A., and Montrose, M. H. (2004) Osmotic regulation of renal betaine transport: transcription and beyond. Pflügers Arch. 449, 227-234
58. Srimaroeng, C., Perry, J. L., and Pritchard, J. B. (2008) Physiology, structure, and regulation of the cloned organic anion transporters. Xenobiotica 38, 889-935
59. Dzurik, R., Spustova, V., Krivosikova, Z., and Gazdikova, K. (2001) Hippurate participates in the correction of metabolic acidosis. Kidney Intl. 78, S278-S281
60. Ferrara, F., Bertelli, A., and Falchi, M. (2005) Evaluation of carnitine, acetylcarnitine and isovalerylcarnitine on immune function and apoptosis. Drugs Exp. Clin. Res. 31, 109-114
61. Pontremoli, S., Melloni, E., Viotti, P. L., Michetti, M., Di Lisa, F., and Siliprandi, N. (1990) Isovalerylcarnitine is a specific activator of the high calcium requiring calpain forms. Biochem. Biophys. Res. Commun. 167, 373-380
62. Carter, A. L., and Frenkel, R. (1978) The relationship of choline and carnitine in the choline deficient rat. J. Nutr. 108, 1748-1754
63. Sheard, N. F., and Krasin, B. (1994) Restricting food intake does not exacerbate the effects of a choline-deficient diet on tissue carnitine concentrations in rats. J. Nutr. 124, 738-743
64. Wagner, C. A., Lukewille, U., Kaltenbach, S., Moschen, I., Broer, A., Risler, T., Broer, S., and Lang, F. (2000) Functional and pharmacological characterization of human Na(+)-carnitine cotransporter hOCTN2. Am. J. Physiol. Renal Physiol. 279, F584-F591
65. Launay-Vacher, V., Izzedine, H., Karie, S., Hulot, J. S., Baumelou, A., and Deray, G. (2006) Renal tubular drug transporters. Nephron 103, 97-106
66. Acara, M., Roch, R. F., and Rennick, B. (1979) Bidirectional renal tubular transport of free choline: a micropuncture study. Am. J. Physiol. 236, F112-F118
67. Urakami, Y., Kimura, N., Okuda, M., and Inui, K. (2004) Creatinine transport by basolateral organic cation transporter hOCT2 in the human kidney. Pharm. Res. 21, 976-981
68. Paillard, F., Catheline, D., Duff, F. L., Bouriel, M., Deugnier, Y., Pouchard, M., Daubert, J. C., and Legrand, P. (2008) Plasma palmitoleic acid, a product of stearoyl-coA desaturase activity, is an independent marker of triglyceridemia and abdominal adiposity. Nutr. Metab. Cardiovasc. Dis. 18, 436-440
69. Attie, A. D., Krauss, R. M., Gray-Keller, M. P., Brownlie, A., Miyazaki, M., Kastelein, J. J., Lusis, A. J., Stalenhoef, A. F., Stoehr, J. P., Hayden, M. R., and Ntambi, J. M. (2002) Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia. J. Lipid Res. 43, 1899-1907
70. Dobrzyn, A., Dobrzyn, P., Miyazaki, M., Sampath, H., Chu, K., and Ntambi, J. M. (2005) Stearoyl-CoA desaturase 1 deficiency increases CTP:choline cytidylyltransferase translocation into the membrane and enhances phosphatidylcholine synthesis in liver. J. Biol. Chem. 280, 23356-23362
71. Kovacic, P. (2005) Unifying mechanism for addiction and toxicity of abused drugs with application to dopamine and glutamate mediators: electron transfer and reactive oxygen species. Med. Hypoth. 65, 90-96
72. Maddox, J. F., Luyendyk, J. P., Cosma, G. N., Breau, A. P., Bible, R. H., Jr., Harrigan, G. G., Goodacre, R., Ganey, P. E., Cantor, G. H., Cockerell, G. L., and Roth, R. A. (2006) Metabonomic evaluation of idiosyncrasy-like liver injury in rats cotreated with ranitidine and lipopolysaccharide. Toxicol. Appl. Pharmacol. 212, 35-44
73. Duarte, I. F., Stanley, E. G., Holmes, E., Lindon, J. C., Gil, A. M., Tang, H., Ferdinand, R., McKee, C. G., Nicholson, J. K., Vilca-Melendez, H., Heaton, N., and Murphy, G. M. (2005) Metabolic assessment of human liver transplants from biopsy samples at the donor and recipient stages using high-resolution magic angle spinning 1H NMR spectroscopy. Anal. Chem. 77, 5570-5578
74. Griffin, J. L., Bonney, S. A., Mann, C., Hebbachi, A. M., Gibbons, G. F., Nicholson, J. K., Shoulders, C. C., and Scott, J. (2004) An integrated reverse functional genomic and metabolic approach to understanding orotic acid-induced fatty liver. Physiol. Genomics 17, 140-149
75. van Ginneken, V., Verhey, E., Poelmann, R., Ramakers, R., van Dijk, K. W., Ham, L., Voshol, P., Havekes, L., Van Eck, M., and van der Greef, J. (2007) Metabolomics (liver and blood profiling) in a mouse model in response to fasting: a study of hepatic steatosis. Biochim. Biophys. Acta 1771, 1263-1270