Transcript and metabolite analysis of the effects of tamoxifen in rat liver reveals inhibition of fatty acid synthesis in the presence of hepatic steatosis

FASEB Journal

Volumn 19, Issue 9, 2005, Pages 1108-1119

  Lelliott, Christopher J ^a   López, Miguel ^a   Curtis, R Keira ^a   Parker, Nadeene ^a,e   Laudes, Matthias ^a   Yeo, Giles ^a   Jimenez Liñan, Mercedes ^a   Grosse, Johannes ^b   Saha, Asish K ^c   Wiggins, David ^d   Hauton, David ^d   Brand, Martin D ^e   O'Rahilly, Stephen ^a   Griffin, Julian L ^a   Gibbons, Geoffrey F ^d   Vidal Puig, Antonio ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b Ingenium Pharmaceuticals AG   (Germany)

^c BOSTON MEDICAL CENTER   (United States)

^d UNIVERSITY OF OXFORD   (United Kingdom)

^e UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Fatty acid synthase; Malonyl CoA; Metabolic pathways; Metabolomics

Indexed keywords

ANTINEOPLASTIC AGENT; CHOLESTEROL; DRUG METABOLITE; FATTY ACID SYNTHASE; MALONYL COENZYME A; SATURATED FATTY ACID; TAMOXIFEN;

ANIMAL TISSUE; ARTICLE; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DOWN REGULATION; FATTY ACID OXIDATION; FATTY ACID SYNTHESIS; FATTY LIVER; GENE EXPRESSION PROFILING; HYPERCHOLESTEROLEMIA; LIPOGENESIS; MALE; MITOCHONDRIAL RESPIRATION; MOLECULAR MECHANICS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; RAT; TRANSCRIPTOMICS;

ANIMALS; BODY WEIGHT; CHOLESTEROL; EATING; FATTY ACID SYNTHETASE COMPLEX; FATTY ACIDS; FATTY LIVER; GENE EXPRESSION PROFILING; HEPATOCYTES; HYDROXYMETHYLGLUTARYL COA REDUCTASES; LIVER; MALE; MALONYL COENZYME A; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; RATS; RATS, WISTAR; RNA, MESSENGER; TAMOXIFEN;

EID: 21744460524     PISSN: 08926638     EISSN: None     Source Type: Journal    
DOI: 10.1096/fj.04-3196com     Document Type: Article

References (41)

1. Ludwig, J., Viggiano, T. R., McGill, D. B., and Oh, B. J. (1980) Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin. Proc. 55, 434-438
2. Chitturi, S., and Farrell, G. C. (2001) Etiopathogenesis of nonalcoholic steatohepatitis. Semin. Liver Dis. 21, 27-41
3. Matteoni, C. A., Younossi, Z. M., Gramlich, T., Boparai, N., Liu, Y. C., and McCullough, A. J. (1999) Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 116, 1413-1419
4. Younossi, Z. M., Diehl, A. M., and Ong, J. P. (2002) Nonalcoholic fatty liver disease: an agenda for clinical research. Hepatology, 35, 746-752
5. Marchesini, G., Brizi, M., Blanchi, G., Tomassetti, S., Bugianesi, E., Lenzi, M., McCullough, A. J., Natale, S., Forlani, G., and Melchionda, N. (2001) Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 50, 1844-1850
6. Sanyal, A. J., Campbell-Sargent, C., Mirshahi, F., Rizzo, W. B., Contos, M. J., Sterling, R. K., Luketic, V. A., Shiftman, M. L., and Clore, J. N. (2001) Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 120, 1183-1192
7. Day, C. P., and James, O. F. (1998) Steatohepatitis: a tale of two "hits"? Gastroenterology 114, 842-845
8. Jaeschke, H., Gores, G. J., Cederbaum, A. I., Hinson, J. A., Pessayre, D., and Lemasters, J. J. (2002) Mechanisms of hepatotoxicity. Toxicol. Sci. 65, 166-176
9. Fromenty, B., Robin, M. A., Igoudjil, A., Mansouri, A., and Pessayre, D. (2004) The ins and outs of mitochondrial dysfunction in NASH. Diabetes Metab. 30, 121-138
10. Pessayre, D., Mansouri, A., and Fromenty, B. (2002) Nonalcoholic steatosis and steatohepatitis. V. Mitochondrial dysfunction in steatohepatitis. Am. J. Physiol. 282, G193-G199
11. Fromenty, B., and Pessayre, D. (1995) Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity. Pharmacol. Ther. 67, 101-154
12. Mensenkamp, A. R., Havekes, L. M., Romijn, J. A., and Kuipers, F. (2001) Hepatic steatosis and very low density lipoprotein secretion: the involvement of apolipoprotein E. J. Hepatol. 35, 816-822
13. Nguyen, M. C., Stewart, R. B., Banerji, M. A., Gordon, D. H., and Kral, J. G. (2001) Relationships between tamoxifen use, liver fat and body fat distribution in women with breast cancer. Int. J. Obes. Relat. Metab. Disord. 25, 296-298
14. Nishino, M., Hayakawa, K., Nakamura, Y., Morimoto, T., and Mukaihara, S. (2003) Effects of tamoxifen on hepatic fat content and the development of hepatic steatosis in patients with breast cancer: high frequency of involvement and rapid reversal after completion of tamoxifen therapy. Am. J. Roentgenol. 180, 129-134
15. Murata, Y., Ogawa, Y., Saibara, T., Nishioka, A., Takeuchi, N., Kariya, S., Onishi, S., and Yoshida, S. (2003) Tamoxifen-induced non-alcoholic steatohepatitis in patients with breast cancer: determination of a suitable biopsy site for diagnosis. Oncol. Rep. 10, 97-100
16. Fisher, B., Costantino, J. P., Wickerham, D. L., Redmond, C. K., Kavanah, M., Cronin, W. M., Vogel, V., Robidoux, A., Dimitrov, N., Atkins, J., et al. (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl. Cancer Inst. 90, 1371-1388
17. Jordan, V. C., Collins, M. M., Rowsby, L., and Prestwich, G. (1977) A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J. Endocrinol. 75, 305-316
18. Jordan, V. C. (2001) Chemoprevention with antiestrogens: the beginning of the end for breast cancer. Daniel G. Miller Lecture. Ann. N. Y. Acad. Sci. 952, 60-72
19. Carthew, P., Edwards, R. E., Nolan, B. M., Martin, E. A., Heydon, R. T., White, I. N., and Tucker, M. J. (2000) Tamoxifen induces endometrial and vaginal cancer in rats in the absence of endometrial hyperplasia. Carcinogenesis 21, 793-797
20. Zhang, W., Couldwell, W. T., Song, H., Takano, T., Lin, J. H., and Nedergaard, M. (2000) Tamoxifen-induced enhancement of calcium signaling in glioma and MCF-7 breast cancer cells. Cancer Res. 60, 5395-5400
21. 13C magic angle spinning NMR spectroscopy of rat liver. Magn. Reson. Med. 44, 201-207
22. Lelliott, C. J., Logie, L., Sewter, C. P., Berger, D., Jani, P., Blows, F., O'Rahilly, S., and Vidal-Puig, A. (2002) Lamin expression in human adipose cells in relation to anatomical site and differentiation state. J. Clin. Endocrinol. Metab. 87, 728-734
23. Vidal-Puig, A. J., Considine, R. V., Jimenez-Linan, M., Werman, A., Pories, W. J., Caro, J. F., and Flier, J. S. (1997) Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J. Clin. Invest. 99, 2416-2422
24. Patti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc. Natl. Acad. Sci. USA 100, 8466-8471
25. Mootha, V. K., Lindgren, C. M., Eriksson, K. F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstrale, M., Laurila, E., et al. (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately down-regulated in human diabetes. Nat. Genet. 34, 267-273
26. Doniger, S. W., Salomonis, N., Dahlquist, K. D., Vranizan, K., Lawlor, S. C., and Conklin, B. R. (2003) MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data. Genome Biol. 4, R7
27. Dahlquist, K. D., Salomonis, N., Vranizan, K., Lawlor, S. C., and Conklin, B. R. (2002) GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nat. Genet. 31, 19-20
28. Harris, M. A., Clark, J., Ireland, A., Lomax, J., Ashburner, M., Foulger, R., Eilbeck, K., Lewis, S., Marshall, B., Mungall, C., et al. (2004) The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 32, D258-D261
29. Bartlett, S. M., and Gibbons, G. F. (1988) Short- and longer-term regulation of very-low-density lipoprotein secretion by insulin, dexamethasone and lipogenic substrates in cultured hepatocytes. A biphasic effect of insulin. Biochem. J. 249, 37-43
30. McGarry, J. D., Stark, M. J., and Foster, D. W. (1978) Hepatic malonyl-CoA levels of fed, fasted and diabetic rats as measured using a simple radioisotopic assay. J. Biol. Chem. 253, 8291-8293
31. Saha, A. K., Kurowski, T. G., and Ruderman, N. B. (1995) A malonyl-CoA fuel-sensing mechanism in muscle: effects of insulin, glucose, and denervation. Am. J. Physiol. 269, E283-E289
32. Wade, G. N., and Heller, H. W. (1993) Tamoxifen mimics the effects of estradiol on food intake, body weight, and body composition in rats. Am. J. Physiol. 264, R1219-R1223
33. Noga, A. A., Zhao, Y., and Vance, D. E. (2002) An unexpected requirement for phosphatidylethanolamine N-methyltransferase in the secretion of very low density lipoproteins. J. Biol. Chem. 277, 42358-42365
34. Nebert, D. W., and Russell, D. W. (2002) Clinical importance of the cytochromes P450. Lancet 360, 1155-1162
35. Berson, A., De Beco, V., Letteron, P., Robin, M. A., Moreau, C., El Kahwaji, J., Verthier, N., Feldmann, G., Fromenty, B., and Pessayre, D. (1998) Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. Gastroenterology 114, 764-774
36. Cardoso, C. M., Custodio, J. B., Almeida, L. M., and Moreno, A. J. (2001) Mechanisms of the deleterious effects of tamoxifen on mitochondrial respiration rate and phosphorylation efficiency. Toxicol. Appl. Pharmacol. 176, 145-152
37. Tuquet, C., Dupont, J., Mesneau, A., and Roussaux, J. (2000) Effects of tamoxifen on the electron transport chain of isolated liver mitochondria. Cell Biol. Toxicol. 16, 207-219
38. 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
39. Rooney, O. M., Troke, J., Nicholson, J. K., and Griffin, J. L. (2003) High-resolution diffusion and relaxation-edited magic angle spinning 1H NMR spectroscopy of intact liver tissue. Magn. Reson. Med. 50, 925-930
40. Yahagi, N., Shimano, H., Hasty, A. H., Matsuzaka, T., Ide, T., Yoshikawa, T., Amemiya-Kudo, M., Tomita, S., Okazaki, H., Tamura, Y., et al. (2002) Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice. J. Biol. Chem. 277, 19353-19357
41. Sekiya, M., Yahagi, N., Matsuzaka, T., Najima, Y., Nakamura, M., Nagai, R., Ishibashi, S., Osuga, J., Yamada, N., and Shimano, H. (2003) Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology 38, 1529-1539