{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:39:55Z","timestamp":1782275995584,"version":"3.54.5"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2013,9,27]],"date-time":"2013-09-27T00:00:00Z","timestamp":1380240000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0075980","type":"journal-article","created":{"date-parts":[[2013,9,27]],"date-time":"2013-09-27T21:10:04Z","timestamp":1380316204000},"page":"e75980","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cerulenin Blockade of Fatty Acid Synthase Reverses Hepatic Steatosis in ob\/ob Mice"],"prefix":"10.1371","volume":"8","author":[{"given":"Gang","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun P.","family":"Palanisamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary P.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alton G.","family":"Sutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inderjit","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold","family":"May","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth D.","family":"Chavin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,9,27]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1055\/s-2001-12926","article-title":"Clinical features and natural history of nonalcoholic steatosis syndromes","volume":"21","author":"Y Falck-Ytter","year":"2001","journal-title":"Semin Liver Dis"},{"key":"ref2","first-page":"52","article-title":"Nonalcoholic fatty liver disease","volume":"70","author":"P Angulo","year":"2005","journal-title":"Rev Gastroenterol Mex"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"S99","DOI":"10.1002\/hep.20973","article-title":"Nonalcoholic fatty liver disease: from steatosis to cirrhosis","volume":"43","author":"GC Farrell","year":"2006","journal-title":"Hepatology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jadohealth.2012.01.010","article-title":"Nonalcoholic fatty liver in children and adolescents: an overview","volume":"51","author":"C Della Corte","year":"2012","journal-title":"J Adolesc Health"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.gassur.2004.04.002","article-title":"Hepatocellular ultrastructure after ischemia\/reperfusion injury in human orthotopic liver transplantation","volume":"8","author":"SN Nadig","year":"2004","journal-title":"J Gastrointest Surg"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1093\/qjmed\/hcg120","article-title":"Non-alcoholic fatty liver: a common manifestation of a metabolic disorder","volume":"96","author":"SD Malnick","year":"2003","journal-title":"QJM"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Begriche K, Massart J, Robin MA, Bonnet F, Fromenty B (2013) Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease. Hepatology.","DOI":"10.1002\/hep.26226"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.3748\/wjg.v19.i8.1158","article-title":"From fatty liver to fibrosis: A tale of \u201csecond hit\u201d","volume":"19","author":"M Basaranoglu","year":"2013","journal-title":"World J Gastroenterol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"G336","DOI":"10.1152\/ajpgi.00049.2011","article-title":"Mitochondrial uncoupling protein-2 deficiency protects steatotic mouse hepatocytes from hypoxia\/reoxygenation","volume":"302","author":"ZP Evans","year":"2012","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1172\/JCI200422422","article-title":"Molecular mediators of hepatic steatosis and liver injury","volume":"114","author":"JD Browning","year":"2004","journal-title":"J Clin Invest"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1097\/00007890-200106270-00018","article-title":"Increased generation of reactive oxygen species in isolated rat fatty liver during postischemic reoxygenation","volume":"71","author":"B Nardo","year":"2001","journal-title":"Transplantation"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"5692","DOI":"10.1074\/jbc.274.9.5692","article-title":"Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion","volume":"274","author":"KD Chavin","year":"1999","journal-title":"J Biol Chem"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"9562","DOI":"10.1074\/jbc.M110132200","article-title":"Mechanism for peroxisome proliferator-activated receptor-alpha activator-induced up-regulation of UCP2 mRNA in rodent hepatocytes","volume":"277","author":"T Nakatani","year":"2002","journal-title":"J Biol Chem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0014-5793(99)00987-4","article-title":"Induction of uncoupling protein (UCP) 2 in primary cultured hepatocytes","volume":"457","author":"K Kimura","year":"1999","journal-title":"FEBS Lett"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1096\/fasebj.14.3.495","article-title":"Effects of fatty acids on uncoupling protein-2 expression in the rat heart","volume":"14","author":"KA Van Der Lee","year":"2000","journal-title":"FASEB J"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1172\/JCI21625","article-title":"Increased oxidative stress in obesity and its impact on metabolic syndrome","volume":"114","author":"S Furukawa","year":"2004","journal-title":"J Clin Invest"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1136\/gut.2005.069757","article-title":"Steatosis in chronic hepatitis C: why does it really matter?","volume":"55","author":"T Asselah","year":"2006","journal-title":"Gut"},{"key":"ref18","doi-asserted-by":"crossref","DOI":"10.1046\/j.1440-1746.17.s1.10.x","article-title":"Non-alcoholic fatty liver disease","volume":"17","author":"P Angulo","year":"2002","journal-title":"J Gastroenterol Hepatol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"10715","DOI":"10.1073\/pnas.0403390101","article-title":"Inhibition of fatty acid synthase (FAS) suppresses HER2\/neu (erbB-2) oncogene overexpression in cancer cells","volume":"101","author":"JA Menendez","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"365","DOI":"10.7164\/antibiotics.25.365","article-title":"Inhibition of sterol and fatty acid biosyntheses by cerulenin in cell-free systems of yeast","volume":"25","author":"S Nomura","year":"1972","journal-title":"J Antibiot (Tokyo)"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0005-2760(73)90241-5","article-title":"Inhibition of fatty acid synthesis by the antibiotic cerulenin. Specific inactivation of beta-ketoacyl-acyl carrier protein synthetase","volume":"326","author":"G D\u2019Agnolo","year":"1973","journal-title":"Biochim Biophys Acta"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"6551","DOI":"10.1074\/jbc.M007101200","article-title":"Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism","volume":"276","author":"AC Price","year":"2001","journal-title":"J Biol Chem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"201S","DOI":"10.1038\/oby.2006.309","article-title":"Fatty acid metabolism, the central nervous system, and feeding","volume":"14","author":"GV Ronnett","year":"2006","journal-title":"Obesity (Silver Spring)"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1126\/science.288.5475.2379","article-title":"Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors","volume":"288","author":"TM Loftus","year":"2000","journal-title":"Science"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"R138","DOI":"10.1152\/ajpregu.00899.2005","article-title":"FAS inhibitor cerulenin reduces food intake and melanocortin receptor gene expression without modulating the other (an)orexigenic neuropeptides in chickens","volume":"291","author":"S Dridi","year":"2006","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1111\/j.1600-6143.2004.00546.x","article-title":"Fatty acid synthase blockade protects steatotic livers from warm ischemia reperfusion injury and transplantation","volume":"4","author":"KD Chavin","year":"2004","journal-title":"Am J Transplant"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2337\/diabetes.50.4.733","article-title":"Cerulenin mimics effects of leptin on metabolic rate, food intake, and body weight independent of the melanocortin system, but unlike leptin, cerulenin fails to block neuroendocrine effects of fasting","volume":"50","author":"H Makimura","year":"2001","journal-title":"Diabetes"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0006-291X(03)01409-8","article-title":"Decrease of intracellular ATP content downregulated UCP2 expression in mouse hepatocytes","volume":"308","author":"G Cheng","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/sj.bjc.6601989","article-title":"Underexpression of peroxisome proliferator-activated receptor (PPAR)gamma in PAX8\/PPARgamma-negative thyroid tumours","volume":"91","author":"AR Marques","year":"2004","journal-title":"Br J Cancer"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"J Folch","year":"1957","journal-title":"J Biol Chem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/0003-2697(90)90208-Q","article-title":"Microtiter plate assay for the measurement of glutathione and glutathione disulfide in large numbers of biological samples","volume":"190","author":"MA Baker","year":"1990","journal-title":"Anal Biochem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.taap.2008.12.023","article-title":"Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles","volume":"236","author":"WS Cho","year":"2009","journal-title":"Toxicol Appl Pharmacol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1016\/j.transproceed.2009.09.055","article-title":"Vitamin E succinate enhances steatotic liver energy status and prevents oxidative damage following ischemia\/reperfusion","volume":"41","author":"ZP Evans","year":"2009","journal-title":"Transplant Proc"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/hep.510290428","article-title":"Mitochondrial proteins that regulate apoptosis and necrosis are induced in mouse fatty liver","volume":"29","author":"A Rashid","year":"1999","journal-title":"Hepatology"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/S0016-5085(99)70022-3","article-title":"Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes","volume":"116","author":"H Cortez-Pinto","year":"1999","journal-title":"Gastroenterology"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1210\/endo.141.11.7771","article-title":"Up-regulation of peroxisome proliferator-activated receptors (PPAR-alpha) and PPAR-gamma messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-gamma-responsive adipose tissue-specific genes in the liver of obese diabetic mice","volume":"141","author":"RA Memon","year":"2000","journal-title":"Endocrinology"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1023\/A:1011927113563","article-title":"Hepatic over-expression of peroxisome proliferator activated receptor gamma2 in the ob\/ob mouse model of non-insulin dependent diabetes mellitus","volume":"224","author":"R Rahimian","year":"2001","journal-title":"Mol Cell Biochem"},{"key":"ref38","first-page":"2745","article-title":"Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells","volume":"56","author":"ES Pizer","year":"1996","journal-title":"Cancer Res"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1006\/bbrc.2001.5146","article-title":"Fatty acid synthase inhibition in human breast cancer cells leads to malonyl-CoA-induced inhibition of fatty acid oxidation and cytotoxicity","volume":"285","author":"JN Thupari","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"ref40","first-page":"131","article-title":"[Establishment of the Chang liver cell line stably overexpressing human UCP2 gene and its effect on mitochondrial membrane potential and reactive oxygen species]","volume":"20","author":"LL Guan","year":"2012","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1006\/jsre.1999.5781","article-title":"Glutathione and ultrastructural changes in inflow occlusion of rat liver","volume":"88","author":"T Armeni","year":"2000","journal-title":"J Surg Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/0092-8674(94)90006-X","article-title":"Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor","volume":"79","author":"P Tontonoz","year":"1994","journal-title":"Cell"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1146\/annurev.physiol.65.092101.142528","article-title":"Nuclear receptors and the control of metabolism","volume":"65","author":"GA Francis","year":"2003","journal-title":"Annu Rev Physiol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"452061","DOI":"10.1155\/2013\/452061","article-title":"Peroxisome proliferator-activated receptor genetic polymorphisms and nonalcoholic Fatty liver disease: any role in disease susceptibility?","volume":"2013","author":"P Dongiovanni","year":"2013","journal-title":"PPAR Res"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Gres S, Canteiro S, Mercader J, Carpene C (2013) Oxidation of high doses of serotonin favors lipid accumulation in mouse and human fat cells. Mol Nutr Food Res.","DOI":"10.1002\/mnfr.201200681"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"de Las Heras N, Valero-Munoz M, Ballesteros S, Gomez-Hernandez A, Martin-Fernandez B, <etal>et al<\/etal>.. (2013) Factors involved in rosuvastatin induction of insulin sensitization in rats fed a high fat diet. Nutr Metab Cardiovasc Dis.","DOI":"10.1016\/j.numecd.2012.11.009"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.bbrc.2013.01.080","article-title":"Characterization of actions of octanoate on porcine preadipocytes and adipocytes differentiated in vitro","volume":"432","author":"S Suzuki","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1038\/sj.ijo.0801492","article-title":"Regulation of adipogenesis and energy balance by PPARgamma and PGC-1","volume":"24","author":"BM Spiegelman","year":"2000","journal-title":"Int J Obes Relat Metab Disord"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev-biochem-052110-115718","article-title":"Adipogenesis: from stem cell to adipocyte","volume":"81","author":"QQ Tang","year":"2012","journal-title":"Annu Rev Biochem"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.tips.2005.03.003","article-title":"PPARs: therapeutic targets for metabolic disease","volume":"26","author":"JP Berger","year":"2005","journal-title":"Trends Pharmacol Sci"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1146\/annurev.med.53.082901.104018","article-title":"The mechanisms of action of PPARs","volume":"53","author":"J Berger","year":"2002","journal-title":"Annu Rev Med"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"10817","DOI":"10.1074\/jbc.M010587200","article-title":"Transcriptional regulation of the mouse uncoupling protein-2 gene. Double E-box motif is required for peroxisome proliferator-activated receptor-gamma-dependent activation","volume":"276","author":"AV Medvedev","year":"2001","journal-title":"J Biol Chem"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1006\/bbrc.1999.0303","article-title":"Increase in uncoupling protein-2 mRNA expression by BRL49653 and bromopalmitate in human adipocytes","volume":"256","author":"N Viguerie-Bascands","year":"1999","journal-title":"Biochem Biophys Res Commun"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1006\/bbrc.1998.9479","article-title":"In vivo effects of pioglitazone on uncoupling protein-2 and -3 mRNA levels in skeletal muscle of hyperglycemic KK mice","volume":"251","author":"T Shimokawa","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"ref55","first-page":"1","article-title":"Toxicological consequences of altered peroxisome proliferator-activated receptor gamma (PPARgamma) expression in the liver: insights from models of obesity and type 2 diabetes","volume":"63","author":"UA Boelsterli","year":"2002","journal-title":"Biochem Pharmacol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1172\/JCI200317223","article-title":"Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes","volume":"111","author":"K Matsusue","year":"2003","journal-title":"J Clin Invest"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"E71","DOI":"10.1152\/ajpendo.00332.2004","article-title":"Respiratory uncoupling by UCP1 and UCP2 and superoxide generation in endothelial cell mitochondria","volume":"288","author":"BD Fink","year":"2005","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/01635581.2013.748923","article-title":"Fatty Acid synthase inhibition induces differential expression of genes involved in apoptosis and cell proliferation in ocular cancer cells","volume":"65","author":"PR Deepa","year":"2013","journal-title":"Nutr Cancer"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"e46484","DOI":"10.1371\/journal.pone.0046484","article-title":"Inhibition of fatty acid metabolism reduces human myeloma cells proliferation","volume":"7","author":"JM Tirado-Velez","year":"2012","journal-title":"PLoS One"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0075980","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T01:33:46Z","timestamp":1646616826000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0075980"}},"subtitle":[],"editor":[{"given":"Rajesh","family":"Mohanraj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,9,27]]},"references-count":59,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2013,9,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0075980","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,27]]}}}