{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:29:13Z","timestamp":1792801753321,"version":"4.5.0"},"reference-count":39,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2004,12]]},"DOI":"10.1124\/jpet.104.072785","type":"journal-article","created":{"date-parts":[[2004,11,18]],"date-time":"2004-11-18T21:03:24Z","timestamp":1100811804000},"page":"864-873","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":52,"title":["Disruption of Hepatic Lipid Homeostasis in Mice after Amiodarone Treatment Is Associated with Peroxisome Proliferator-Activated Receptor-\u03b1Target Gene Activation"],"prefix":"10.1016","volume":"311","author":[{"given":"Tanya C.","family":"McCarthy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Timothy","family":"Pollak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyisha A.","family":"Hanniman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Sinal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.104.072785_bib1","doi-asserted-by":"crossref","unstructured":"Aoyama T, Peters JM, Iritani N, Nakajima T, Furihata K, Hashimoto T, and Gonzalez FJ (1998) Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPARalpha). J Biol Chem 273: 5678\u20135684.","DOI":"10.1074\/jbc.273.10.5678"},{"key":"10.1124\/jpet.104.072785_bib2","doi-asserted-by":"crossref","unstructured":"Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, Staels B, Auwerx J, Laville M, and Vidal H (1997) Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients. Diabetes 46: 1319\u20131327.","DOI":"10.2337\/diab.46.8.1319"},{"key":"10.1124\/jpet.104.072785_bib3","doi-asserted-by":"crossref","unstructured":"Bolt MW, Card JW, Racz WJ, Brien JF, and Massey TE (2001) Disruption of mitochondrial function and cellular ATP levels by amiodarone and N-desethylamiodarone in initiation of amiodarone-induced pulmonary cytotoxicity. J Pharmacol Exp Ther 298: 1280\u20131289.","DOI":"10.1016\/S0022-3565(24)29503-3"},{"key":"10.1124\/jpet.104.072785_bib4","doi-asserted-by":"crossref","unstructured":"Bonnefont JP, Demaugre F, Prip-Buus C, Saudubray JM, Brivet M, Abadi N, and Thuillier L (1999) Carnitine palmitoyltransferase deficiencies. Mol Genet Metab 68: 424\u2013440.","DOI":"10.1006\/mgme.1999.2938"},{"key":"10.1124\/jpet.104.072785_bib5","doi-asserted-by":"crossref","unstructured":"Burkart F, Pfisterer M, Kiowski W, Follath F, and Burckhardt D (1990) Effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias: Basel Antiarrhythmic Study of Infarct Survival (BASIS). J Am Coll Cardiol 16: 1711\u20131718.","DOI":"10.1016\/0735-1097(90)90324-I"},{"key":"10.1124\/jpet.104.072785_bib6","doi-asserted-by":"crossref","unstructured":"Card JW, Lalonde BR, Rafeiro E, Tam AS, Racz WJ, Brien JF, Bray TM, and Massey TE (1998) Amiodarone-induced disruption of hamster lung and liver mitochondrial function: lack of association with thiobarbituric acid-reactive substance production. Toxicol Lett 98: 41\u201350.","DOI":"10.1016\/S0378-4274(98)00097-6"},{"key":"10.1124\/jpet.104.072785_bib7","doi-asserted-by":"crossref","unstructured":"Doval HC, Nul DR, Grancelli HO, Perrone SV, Bortman GR, and Curiel R (1994) Randomised trial of low-dose amiodarone in severe congestive heart failure. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA). Lancet 344: 493\u2013498.","DOI":"10.1016\/S0140-6736(94)91895-3"},{"key":"10.1124\/jpet.104.072785_bib8","doi-asserted-by":"crossref","unstructured":"Escher P, Braissant O, Basu-Modak S, Michalik L, Wahli W, and Desvergne B (2001) Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology 142: 4195\u20134202.","DOI":"10.1210\/endo.142.10.8458"},{"key":"10.1124\/jpet.104.072785_bib9","doi-asserted-by":"crossref","unstructured":"Francis GA, Annicotte JS, and Auwerx J (2003a) PPAR agonists in the treatment of atherosclerosis. Curr Opin Pharmacol 3: 186\u2013191.","DOI":"10.1016\/S1471-4892(03)00014-6"},{"key":"10.1124\/jpet.104.072785_bib10","doi-asserted-by":"crossref","unstructured":"Francis GA, Fayard E, Picard F, and Auwerx J (2003b) Nuclear receptors and the control of metabolism. Annu Rev Physiol 65: 261\u2013311.","DOI":"10.1146\/annurev.physiol.65.092101.142528"},{"key":"10.1124\/jpet.104.072785_bib11","doi-asserted-by":"crossref","unstructured":"Fromenty B, Fisch C, Labbe G, Degott C, Deschamps D, Berson A, Letteron P, and Pessayre D (1990) Amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice. J Pharmacol Exp Ther 255: 1371\u20131376.","DOI":"10.1016\/S0022-3565(25)22984-6"},{"key":"10.1124\/jpet.104.072785_bib12","doi-asserted-by":"crossref","unstructured":"Fromenty B and Pessayre D (1995) Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity. Pharmacol Ther 67: 101\u2013154.","DOI":"10.1016\/0163-7258(95)00012-6"},{"key":"10.1124\/jpet.104.072785_bib13","doi-asserted-by":"crossref","unstructured":"Gill J, Heel RC, and Fitton A (1992) Amiodarone. An overview of its pharmacological properties and review of its therapeutic use in cardiac arrhythmias. Drugs 43: 69\u2013110.","DOI":"10.2165\/00003495-199243010-00007"},{"key":"10.1124\/jpet.104.072785_bib14","doi-asserted-by":"crossref","unstructured":"Ip E, Farrell G, Hall P, Robertson G, and Leclercq I (2004) Administration of the potent PPARalpha agonist, Wy-14,643, reverses nutritional fibrosis and steatohepatitis in mice. Hepatology 39: 1286\u20131296.","DOI":"10.1002\/hep.20170"},{"key":"10.1124\/jpet.104.072785_bib15","doi-asserted-by":"crossref","unstructured":"Ip E, Farrell GC, Robertson G, Hall P, Kirsch R, and Leclercq I (2003) Central role of PPARalpha-dependent hepatic lipid turnover in dietary steatohepatitis in mice. Hepatology 38: 123\u2013132.","DOI":"10.1053\/jhep.2003.50307"},{"key":"10.1124\/jpet.104.072785_bib16","doi-asserted-by":"crossref","unstructured":"Kennedy JA, Unger SA, and Horowitz JD (1996) Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochem Pharmacol 52: 273\u2013280.","DOI":"10.1016\/0006-2952(96)00204-3"},{"key":"10.1124\/jpet.104.072785_bib17","unstructured":"Khairy P and Nattel S (2002) New insights into the mechanisms and management of atrial fibrillation. Can Med Assoc J 167: 1012\u20131020."},{"key":"10.1124\/jpet.104.072785_bib18","doi-asserted-by":"crossref","unstructured":"Koteish A and Diehl AM (2001) Animal models of steatosis. Semin Liver Dis 21: 89\u2013104.","DOI":"10.1055\/s-2001-12932"},{"key":"10.1124\/jpet.104.072785_bib19","doi-asserted-by":"crossref","unstructured":"Latini R, Reginato R, Burlingame AL, and Kates RE (1984) High-performance liquid chromatographic isolation and fast atom bombardment mass spectrometric identification of di-N-desethylamiodarone, a new metabolite of amiodarone in the dog. Biomed Mass Spectrom 11: 466\u2013471.","DOI":"10.1002\/bms.1200110906"},{"key":"10.1124\/jpet.104.072785_bib20","doi-asserted-by":"crossref","unstructured":"Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, Westphal H, and Gonzalez FJ (1995) Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 15: 3012\u20133022.","DOI":"10.1128\/MCB.15.6.3012"},{"key":"10.1124\/jpet.104.072785_bib21","doi-asserted-by":"crossref","unstructured":"Letteron P, Sutton A, Mansouri A, Fromenty B, and Pessayre D (2003) Inhibition of microsomal triglyceride transfer protein: another mechanism for drug-induced steatosis in mice. Hepatology 38: 133\u2013140.","DOI":"10.1053\/jhep.2003.50309"},{"key":"10.1124\/jpet.104.072785_bib22","doi-asserted-by":"crossref","unstructured":"Mascaro C, Acosta E, Ortiz JA, Rodriguez JC, Marrero PF, Hegardt FG, and Haro D (1999) Characterization of a response element for peroxisomal proliferator activated receptor (PPRE) in human muscle-type carnitine palmitoyltransferase I. Adv Exp Med Biol 466: 79\u201385.","DOI":"10.1007\/0-306-46818-2_8"},{"key":"10.1124\/jpet.104.072785_bib23","doi-asserted-by":"crossref","unstructured":"Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, Sterling RK, Shiffman ML, Stravitz RT, and Sanyal AJ (2003) Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 37: 1286\u20131292.","DOI":"10.1053\/jhep.2003.50229"},{"key":"10.1124\/jpet.104.072785_bib24","doi-asserted-by":"crossref","unstructured":"Pollak PT (1996) A systematic review and critical comparison of internal standards for the routine liquid chromatographic assay of amiodarone and desethylamiodarone. Ther Drug Monit 18: 168\u2013178.","DOI":"10.1097\/00007691-199604000-00011"},{"key":"10.1124\/jpet.104.072785_bib25","unstructured":"Rao MS, Papreddy K, Musunuri S, and Okonkwo A (2002) Prevention\/reversal of choline deficiency-induced steatohepatitis by a peroxisome proliferator-activated receptor alpha ligand in rats. In Vivo 16: 145\u2013152."},{"key":"10.1124\/jpet.104.072785_bib26","doi-asserted-by":"crossref","unstructured":"Reddy JK and Hashimoto T (2001) Peroxisomal beta-oxidation and peroxisome proliferator-activated receptor alpha: an adaptive metabolic system. Annu Rev Nutr 21: 193\u2013230.","DOI":"10.1146\/annurev.nutr.21.1.193"},{"key":"10.1124\/jpet.104.072785_bib27","doi-asserted-by":"crossref","unstructured":"Richer M and Robert S (1995) Fatal hepatotoxicity following oral administration of amiodarone. Ann Pharmacother 29: 582\u2013586.","DOI":"10.1177\/106002809502900605"},{"key":"10.1124\/jpet.104.072785_bib28","doi-asserted-by":"crossref","unstructured":"Rigas B, Rosenfeld LE, Barwick KW, Enriquez R, Helzberg J, Batsford WP, Josephson ME, and Riely CA (1986) Amiodarone hepatotoxicity. A clinicopathologic study of five patients. Ann Intern Med 104: 348\u2013351.","DOI":"10.7326\/0003-4819-104-3-348"},{"key":"10.1124\/jpet.104.072785_bib29","doi-asserted-by":"crossref","unstructured":"Shinagawa K, Shiroshita-Takeshita A, Schram G, and Nattel S (2003) Effects of antiarrhythmic drugs on fibrillation in the remodeled atrium: insights into the mechanism of the superior efficacy of amiodarone. Circulation 107: 1440\u20131446.","DOI":"10.1161\/01.CIR.0000055316.35552.74"},{"key":"10.1124\/jpet.104.072785_bib30","doi-asserted-by":"crossref","unstructured":"Simon JB, Manley PN, Brien JF, and Armstrong PW (1984) Amiodarone hepatotoxicity simulating alcoholic liver disease. N Engl J Med 311: 167\u2013172.","DOI":"10.1056\/NEJM198407193110308"},{"key":"10.1124\/jpet.104.072785_bib31","doi-asserted-by":"crossref","unstructured":"Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, and Gonzalez FJ (2000) Targeted disruption of the nuclear receptor FXR\/BAR impairs bile acid and lipid homeostasis. Cell 102: 731\u2013744.","DOI":"10.1016\/S0092-8674(00)00062-3"},{"key":"10.1124\/jpet.104.072785_bib32","doi-asserted-by":"crossref","unstructured":"Sinal CJ, Yoon M, and Gonzalez FJ (2001) Antagonism of the actions of peroxisome proliferator-activated receptor-alpha by bile acids. J Biol Chem 276: 47154\u201347162.","DOI":"10.1074\/jbc.M107000200"},{"key":"10.1124\/jpet.104.072785_bib33","doi-asserted-by":"crossref","unstructured":"Spaniol M, Bracher R, Ha HR, Follath F, and Krahenbuhl S (2001) Toxicity of amiodarone and amiodarone analogues on isolated rat liver mitochondria. J Hepatol 35: 628\u2013636.","DOI":"10.1016\/S0168-8278(01)00189-1"},{"key":"10.1124\/jpet.104.072785_bib34","doi-asserted-by":"crossref","unstructured":"Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, and Fruchart JC (1998) Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 98: 2088\u20132093.","DOI":"10.1161\/01.CIR.98.19.2088"},{"key":"10.1124\/jpet.104.072785_bib35","doi-asserted-by":"crossref","unstructured":"Staels B, Vu-Dac N, Kosykh VA, Saladin R, Fruchart JC, Dallongeville J, and Auwerx J (1995) Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. A potential mechanism for the hypolipidemic action of fibrates. J Clin Investig 95: 705\u2013712.","DOI":"10.1172\/JCI117717"},{"key":"10.1124\/jpet.104.072785_bib36","doi-asserted-by":"crossref","unstructured":"Stravitz RT and Sanyal AJ (2003) Drug-induced steatohepatitis. Clin Liver Dis 7: 435\u2013451.","DOI":"10.1016\/S1089-3261(03)00027-8"},{"key":"10.1124\/jpet.104.072785_bib37","doi-asserted-by":"crossref","unstructured":"Wahli W, Devchand PR, IJpenberg A, and Desvergne B (1999) Fatty acids, eicosanoids and hypolipidemic agents regulate gene expression through direct binding to peroxisome proliferator-activated receptors. Adv Exp Med Biol 447: 199\u2013209.","DOI":"10.1007\/978-1-4615-4861-4_19"},{"key":"10.1124\/jpet.104.072785_bib38","doi-asserted-by":"crossref","unstructured":"Wolfrum C, Borrmann CM, Borchers T, and Spener F (2001) Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors alpha- and gamma-mediated gene expression via liver fatty acid binding protein: a signaling path to the nucleus. Proc Natl Acad Sci USA 98: 2323\u20132328.","DOI":"10.1073\/pnas.051619898"},{"key":"10.1124\/jpet.104.072785_bib39","doi-asserted-by":"crossref","unstructured":"Xie Y, Yang Q, and DePierre JW (2002) The effects of peroxisome proliferators on global lipid homeostasis and the possible significance of these effects to other responses to these xenobiotics: an hypothesis. Ann NY Acad Sci 973: 17\u201325.","DOI":"10.1111\/j.1749-6632.2002.tb04600.x"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524316672?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524316672?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.104.072785","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T16:05:13Z","timestamp":1739981113000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524316672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2004,12]]}},"alternative-id":["S0022356524316672"],"URL":"https:\/\/doi.org\/10.1124\/jpet.104.072785","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2004,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Disruption of Hepatic Lipid Homeostasis in Mice after Amiodarone Treatment Is Associated with Peroxisome Proliferator-Activated Receptor-\u03b1Target Gene Activation","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.104.072785","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2004 The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}