fax: 780-492-3383
Steatohepatitis/Metabolic Liver Disease
You have full text access to this OnlineOpen article
Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis†
Article first published online: 16 JUN 2010
DOI: 10.1002/hep.23813
Copyright © 2010 American Association for the Study of Liver Diseases
Additional Information
How to Cite
Cole, L. K., Jacobs, R. L. and Vance, D. E. (2010), Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis. Hepatology, 52: 1258–1265. doi: 10.1002/hep.23813
- †
Potential conflict of interest: Nothing to report.
- ‡
fax: 780-492-3383
Publication History
- Issue published online: 16 JUN 2010
- Article first published online: 16 JUN 2010
- Manuscript Accepted: 9 JUN 2010
- Manuscript Received: 9 FEB 2010
Funded by
- Canadian Institutes of Health Research. Grant Number: MOP 5182
- Dennis E. Vance is a scientist with the Alberta Heritage Foundation for Medical Research
References
- 1. The development of tamoxifen for breast cancer therapy: a tribute to the late Arthur L. Walpole. Breast Cancer Res Treat 1988; 11: 197-209.
- 2, , , , , , et al. SEER Cancer Statistics Review, 1975-2006. Bethesda, MD: National Cancer Institute; 2009.
- 3Early Breast Cancer Trialists' Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998; 351: 1451-1467.
- 4, , . The multiple applications of tamoxifen: an example pointing to SERM modulation being the aspirin of the 21st century. Med Sci Monit 2008; 14: RA144-RA148.
- 5. Antiestrogens—tamoxifen, SERMs and beyond. Invest New Drugs 1999; 17: 285-311.
- 6, , . Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis. Hum Reprod 2005; 20: 1511-1515.
- 7, , , , , , et al. Ovulation induction with tamoxifen and alternate-day gonadotrophin in patients with thin endometrium. Reprod Biomed Online 2008; 17: 20-26.
- 8, , , , , , et al. Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial. Ann Oncol 2009; 20: 1489-1498.
- 9, , , , . 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. AJR Am J Roentgenol 2003; 180: 129-134.
- 10, , , , , , et al. Unrecognized hepatic steatosis and non-alcoholic steatohepatitis in adjuvant tamoxifen for breast cancer patients. Oncol Rep 2000; 7: 1299-1304.
- 11, , , , , , et al. Cirrhosis with steatohepatitis after adjuvant tamoxifen. Lancet 1999; 353: 36-37.
- 12, , , , , , et al. Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial. BMJ 2005; 330: 932.
- 13, , , , , , et al. Tamoxifen inhibits topoisomerases, depletes mitochondrial DNA, and triggers steatosis in mouse liver. J Pharmacol Exp Ther 2007; 321: 526-535.
- 14, , , , , , et al. 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 J 2005; 19: 1108-1119.
- 15, , . Causes and prevention of tamoxifen-induced accumulation of triacylglycerol in rat liver. J Lipid Res 2006; 47: 2223-2232.
- 16, . Tamoxifen mimics the effects of estradiol on food intake, body weight, and body composition in rats. Am J Physiol 1993; 264: R1219-R1223.
- 17, . A gender-specific role for phosphatidylethanolamine N-methyltransferase-derived phosphatidylcholine in the regulation of plasma high density and very low density lipoproteins in mice. J Biol Chem 2003; 278: 21851-21859.
- 18, , . An unexpected requirement for phosphatidylethanolamine N-methyltransferase in the secretion of very low density lipoproteins. J Biol Chem 2002; 277: 42358-42365.
- 19, , , , , , et al. Lack of phosphatidylethanolamine N-methyltransferase alters plasma VLDL phospholipids and attenuates atherosclerosis in mice. Arterioscler Thromb Vasc Biol 2009; 29: 1349-1355.
- 20, . Nascent VLDL phospholipid composition is altered when phosphatidylcholine biosynthesis is inhibited: evidence for a novel mechanism that regulates VLDL secretion. Biochim Biophys Acta 1995; 1258: 159-168.
- 21, , , , . Impaired biosynthesis of phosphatidylcholine causes a decrease in the number of very low density lipoprotein particles in the Golgi but not in the endoplasmic reticulum of rat liver. J Biol Chem 1993; 268: 24990-24996.
- 22, . A role for Sp1 in transcriptional regulation of phosphatidylethanolamine N-methyltransferase in liver and 3T3-L1 adipocytes. J Biol Chem 2010; 285: 11880-11891.
- 23, , , , , . Mouse liver cell culture. I. Hepatocyte isolation. In Vitro 1981; 17: 913-925.
- 24, . A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1959; 37: 911-917.
- 25, , , , , , et al. AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives. Acta Physiol (Oxf) 2009; 196: 81-98.
- 26, , , , . Role of reversible phosphorylation of acetyl-CoA carboxylase in long-chain fatty acid synthesis. FASEB J 1989; 3: 2250-2256.
- 27, , , , , . Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J Biol Chem 2005; 280: 35983-35991.
- 28, , , , , , et al. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 1998; 95: 927-937.
- 29, , , . The ins and outs of GPR30: a transmembrane estrogen receptor. J Steroid Biochem Mol Biol 2008; 109: 350-353.
- 30, , , , , , et al. EGFR activation confers protections against UV-induced apoptosis in cultured mouse skin dendritic cells. Cell Signal 2008; 20: 1830-1838.
- 31, , , , . Regulation of AMP-activated protein kinase by cAMP in adipocytes: roles for phosphodiesterases, protein kinase B, protein kinase A, Epac and lipolysis. Cell Signal 2009; 21: 760-766.
- 32, , , , , , et al. Hepatic stearoyl-CoA desaturase (SCD)-1 activity and diacylglycerol but not ceramide concentrations are increased in the nonalcoholic human fatty liver. Diabetes 2009; 58: 203-208.
- 33, , , , , , et al. Effects of estrogen and androgen deprivation on the progression of non-alcoholic steatohepatitis (NASH) in male Sprague-Dawley rats. Hepatol Res 2009; 39: 910-920.
- 34, , , , . Effects of ovariectomy on PPAR alpha, SREBP-1c, and SCD-1 gene expression in the rat liver. Menopause 2008; 15: 1169-1175.
- 35, , . Tamoxifen decreases cholesterol sevenfold and abolishes lipid lesion development in apolipoprotein E knockout mice. Circulation 1997; 95: 1542-1548.
- 36, , , . Biochemical and evolutionary significance of phospholipid methylation. J Biol Chem 1998; 273: 27043-27046.
- 37, . Molecular links between obesity and breast cancer. Endocr Relat Cancer 2006; 13: 279-292.
- 38, , . Non-alcoholic fatty liver disease is associated with cardiovascular disease risk markers. Obes Rev 2009; 10: 412-419.

1527-3350/asset/olbannerleft.gif?v=1&s=4b2409f9534ed500d3c8da1940a23842e2b9932d)
1527-3350/asset/olbannerright.gif?v=1&s=141b9a8485298533c3e2016e937b0404f7d933e1)
