{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:20:57Z","timestamp":1783700457980,"version":"3.55.0"},"reference-count":51,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":366,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1C1B5015716"],"award-info":[{"award-number":["2017R1C1B5015716"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1I1A2A01060031"],"award-info":[{"award-number":["2019R1I1A2A01060031"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ajp.amjpathol.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Pathology"],"published-print":{"date-parts":[[2021,9]]},"DOI":"10.1016\/j.ajpath.2021.05.020","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T11:16:41Z","timestamp":1623410201000},"page":"1550-1563","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":25,"title":["Vitamin C Deficiency Inhibits Nonalcoholic Fatty Liver Disease Progression through Impaired de Novo Lipogenesis"],"prefix":"10.1016","volume":"191","author":[{"given":"Seoung-Woo","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Min","family":"Baek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Ku","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A-Rang","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Un","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Kyoon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon-Seok","family":"Roh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il-Hwa","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Joon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Hwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-Shik","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4876-1055","authenticated-orcid":false,"given":"Jin-Kyu","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajpath.2021.05.020_bib1","doi-asserted-by":"crossref","first-page":"14219","DOI":"10.3748\/wjg.v20.i39.14219","article-title":"Non-alcoholic fatty liver disease: what has changed in the treatment since the beginning?","volume":"20","author":"Baran","year":"2014","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.ajpath.2021.05.020_bib2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11901-015-0263-9","article-title":"Noninvasive testing for NASH and NASH with advanced fibrosis: are we there yet?","volume":"14","author":"Arulanandan","year":"2015","journal-title":"Curr Hepatol Rep"},{"key":"10.1016\/j.ajpath.2021.05.020_bib3","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nrgastro.2013.183","article-title":"NAFLD, NASH and liver cancer","volume":"10","author":"Michelotti","year":"2013","journal-title":"Nat Rev Gastroenterol"},{"key":"10.1016\/j.ajpath.2021.05.020_bib4","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1172\/JCI8814","article-title":"CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis","volume":"105","author":"Leclercq","year":"2000","journal-title":"J Clin Invest"},{"key":"10.1016\/j.ajpath.2021.05.020_bib5","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bbalip.2009.10.007","article-title":"Fatty liver and lipotoxicity","volume":"1801","author":"Trauner","year":"2010","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"10.1016\/j.ajpath.2021.05.020_bib6","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10809","article-title":"Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity","volume":"482","author":"Henao-Mejia","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.ajpath.2021.05.020_bib7","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrgastro.2013.41","article-title":"Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis","volume":"10","author":"Anstee","year":"2013","journal-title":"Nat Rev Gastroenterol"},{"key":"10.1016\/j.ajpath.2021.05.020_bib8","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1055\/s-0028-1091978","article-title":"The epidemiology of nonalcoholic fatty liver disease: a global perspective","volume":"28","author":"Lazo","year":"2008","journal-title":"Semin Liver Dis"},{"key":"10.1016\/j.ajpath.2021.05.020_bib9","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/hep.20466","article-title":"Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity","volume":"40","author":"Browning","year":"2004","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2021.05.020_bib10","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4254\/wjh.v9.i16.715","article-title":"Non-alcoholic fatty liver disease: an expanded review","volume":"9","author":"Benedict","year":"2017","journal-title":"World J Hepatol"},{"key":"10.1016\/j.ajpath.2021.05.020_bib11","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/0304-4165(92)90108-7","article-title":"Purification of senescence marker protein-30 (SMP30) and its androgen-independent decrease with age in the rat liver","volume":"1116","author":"Fujita","year":"1992","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.ajpath.2021.05.020_bib12","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1515\/BMC.2011.041","article-title":"Senescence marker protein 30: functional and structural insights to its unknown physiological function","volume":"2","author":"Scott","year":"2011","journal-title":"Biomol Concepts"},{"key":"10.1016\/j.ajpath.2021.05.020_bib13","first-page":"S88","article-title":"Pathophysiological significance of senescence marker protein-30","volume":"10","author":"Maruyama","year":"2010","journal-title":"Gerontol Geriatr Med"},{"key":"10.1016\/j.ajpath.2021.05.020_bib14","doi-asserted-by":"crossref","first-page":"5723","DOI":"10.1073\/pnas.0511225103","article-title":"Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy","volume":"103","author":"Kondo","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2021.05.020_bib15","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1080\/07315724.2003.10719272","article-title":"Vitamin C as an antioxidant: evaluation of its role in disease prevention","volume":"22","author":"Padayatty","year":"2003","journal-title":"J Am Coll Nutr"},{"key":"10.1016\/j.ajpath.2021.05.020_bib16","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/180553a0","article-title":"Missing step in man, monkey and guinea pig required for the biosynthesis of L-ascorbic acid","volume":"180","author":"Burns","year":"1957","journal-title":"Nature"},{"key":"10.1016\/j.ajpath.2021.05.020_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1423-0127-19-26","article-title":"Amelioration of diet-induced nonalcoholic steatohepatitis in rats by Mn-salen complexes via reduction of oxidative stress","volume":"19","author":"Rezazadeh","year":"2012","journal-title":"J Biomed Sci"},{"key":"10.1016\/j.ajpath.2021.05.020_bib18","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.3390\/nu9111211","article-title":"Vitamin C and immune function","volume":"9","author":"Carr","year":"2017","journal-title":"Nutrients"},{"key":"10.1016\/j.ajpath.2021.05.020_bib19","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"10.1016\/j.ajpath.2021.05.020_bib20","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.cell.2018.08.020","article-title":"ER stress drives lipogenesis and steatohepatitis via caspase-2 activation of S1P","volume":"175","author":"Kim","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.ajpath.2021.05.020_bib21","doi-asserted-by":"crossref","first-page":"5473","DOI":"10.3390\/nu6125473","article-title":"Does vitamin C deficiency promote fatty liver disease development?","volume":"6","author":"Ipsen","year":"2014","journal-title":"Nutrients"},{"key":"10.1016\/j.ajpath.2021.05.020_bib22","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3390\/medicina56100544","article-title":"Silymarin in combination with vitamin C, vitamin E, coenzyme Q10 and selenomethionine to improve liver enzymes and blood lipid profile in NAFLD patients","volume":"56","author":"Curcio","year":"2020","journal-title":"Medicina"},{"key":"10.1016\/j.ajpath.2021.05.020_bib23","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2021.05.020_bib24","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s10456-020-09717-x","article-title":"Free fatty acid receptor 4 activation protects against choroidal neovascularization in mice","volume":"23","author":"Tomita","year":"2020","journal-title":"Angiogenesis"},{"key":"10.1016\/j.ajpath.2021.05.020_bib25","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jhep.2010.10.024","article-title":"Distinct regulation of adiponutrin\/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in mouse and human hepatocytes","volume":"55","author":"Dubuquoy","year":"2011","journal-title":"J Hepatol"},{"key":"10.1016\/j.ajpath.2021.05.020_bib26","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.metabol.2011.11.008","article-title":"Antisense reduction of 11\u03b2-hydroxysteroid dehydrogenase type 1 enhances energy expenditure and insulin sensitivity independent of food intake in C57BL\/6J mice on a western-type diet","volume":"61","author":"Li","year":"2012","journal-title":"Metabolism"},{"key":"10.1016\/j.ajpath.2021.05.020_bib27","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1038\/aps.2016.46","article-title":"Betulin attenuates atherosclerosis in apoE\u2212\/\u2212 mice by up-regulating ABCA1 and ABCG1","volume":"37","author":"Gui","year":"2016","journal-title":"Acta Pharmacol Sin"},{"key":"10.1016\/j.ajpath.2021.05.020_bib28","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ab.2009.09.040","article-title":"Keeping the intracellular vitamin C at a physiologically relevant level in endothelial cell culture","volume":"397","author":"Frikke-Schmidt","year":"2010","journal-title":"Anal Biochem"},{"key":"10.1016\/j.ajpath.2021.05.020_bib29","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3109\/10409231003667500","article-title":"Genetic control of de novo lipogenesis: role in diet-induced obesity","volume":"45","author":"Strable","year":"2010","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"10.1016\/j.ajpath.2021.05.020_bib30","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1463-1326.2010.01275.x","article-title":"Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c","volume":"12","author":"Ferre","year":"2010","journal-title":"Diabetes Obes Metab"},{"key":"10.1016\/j.ajpath.2021.05.020_bib31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0092-8674(94)90234-8","article-title":"SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis","volume":"77","author":"Wang","year":"1994","journal-title":"Cell"},{"key":"10.1016\/j.ajpath.2021.05.020_bib32","doi-asserted-by":"crossref","first-page":"12975","DOI":"10.1073\/pnas.94.24.12975","article-title":"Coordinate regulation of lipogenic gene expression by androgens: evidence for a cascade mechanism involving sterol regulatory element binding proteins","volume":"94","author":"Swinnen","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2021.05.020_bib33","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0092-8674(00)80213-5","article-title":"The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor","volume":"89","author":"Brown","year":"1997","journal-title":"Cell"},{"key":"10.1016\/j.ajpath.2021.05.020_bib34","first-page":"49","article-title":"Aggravation of cholesterol induced hyperlipidemia by chronic vitamin C deficiency: experimental study in guinea pigs","volume":"39","author":"Kothari","year":"1988","journal-title":"Acta Bot Hung"},{"key":"10.1016\/j.ajpath.2021.05.020_bib35","doi-asserted-by":"crossref","first-page":"C1220","DOI":"10.1152\/ajpcell.00348.2009","article-title":"Hepatocyte nuclear factor 1 is essential for transcription of sodium-dependent vitamin C transporter protein 1","volume":"297","author":"Michels","year":"2009","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.ajpath.2021.05.020_bib36","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1002\/hep.27964","article-title":"Negative feedback regulation of bile acid metabolism: impact on liver metabolism and diseases","volume":"62","author":"Chiang","year":"2015","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2021.05.020_bib37","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S0899-3467(07)60127-X","article-title":"The efficacy of vitamin C supplementation on reducing total serum cholesterol in human subjects: a review and analysis of 51 experimental trials","volume":"5","author":"McRae","year":"2006","journal-title":"J Chiropr Med"},{"key":"10.1016\/j.ajpath.2021.05.020_bib38","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jcme.2008.01.002","article-title":"Vitamin C supplementation lowers serum low-density lipoprotein cholesterol and triglycerides: a meta-analysis of 13 randomized controlled trials","volume":"7","author":"McRae","year":"2008","journal-title":"J Chiropr Med"},{"key":"10.1016\/j.ajpath.2021.05.020_bib39","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1126\/science.179.4074.702","article-title":"Cholesterol: vitamin C controls its transformation to bile acids","volume":"179","author":"Ginter","year":"1973","journal-title":"Science"},{"key":"10.1016\/j.ajpath.2021.05.020_bib40","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/S0006-291X(77)80081-8","article-title":"Hypovitaminosis C and cholelithiasis in guinea pigs","volume":"77","author":"Jenkins","year":"1977","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.ajpath.2021.05.020_bib41","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev.genet.41.110306.130315","article-title":"Regulation of sterol synthesis in eukaryotes","volume":"41","author":"Espenshade","year":"2007","journal-title":"Annu Rev Genet"},{"key":"10.1016\/j.ajpath.2021.05.020_bib42","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1007\/s10495-007-0172-7","article-title":"Caspase-2 activation in neural stem cells undergoing oxidative stress-induced apoptosis","volume":"13","author":"Tamm","year":"2008","journal-title":"Apoptosis"},{"key":"10.1016\/j.ajpath.2021.05.020_bib43","doi-asserted-by":"crossref","first-page":"7019573","DOI":"10.1155\/2018\/7019573","article-title":"Treatment of NASH with antioxidant therapy: beneficial effect of red cabbage on type 2 diabetic rats","volume":"2018","author":"Dal","year":"2018","journal-title":"Oxid Med Cell Longev"},{"key":"10.1016\/j.ajpath.2021.05.020_bib44","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1053\/jhep.2003.50132","article-title":"Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis","volume":"37","author":"Musso","year":"2003","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2021.05.020_bib45","first-page":"277","article-title":"Clinical, biochemical and histological correlations in a group of non-drinker subjects with non-alcoholic fatty liver disease","volume":"70","author":"Canbakan","year":"2007","journal-title":"Acta Gastroenterol Belg"},{"key":"10.1016\/j.ajpath.2021.05.020_bib46","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1097\/01.mcg.0000212608.59090.08","article-title":"Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD)","volume":"40","author":"Madan","year":"2006","journal-title":"J Clin Gastroenterol"},{"key":"10.1016\/j.ajpath.2021.05.020_bib47","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/MPG.0b013e318229da1a","article-title":"Correlation of vitamin E, uric acid and diet composition with histologic features of pediatric nonalcoholic fatty liver disease","volume":"54","author":"Vos","year":"2012","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"10.1016\/j.ajpath.2021.05.020_bib48","doi-asserted-by":"crossref","first-page":"8263","DOI":"10.3748\/wjg.v23.i47.8263","article-title":"Clinical epidemiology and disease burden of nonalcoholic fatty liver disease","volume":"23","author":"Perumpail","year":"2017","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.ajpath.2021.05.020_bib49","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/jgh.12271","article-title":"Characteristics and diagnosis of NAFLD\/NASH","volume":"28","author":"Hashimoto","year":"2013","journal-title":"J Gastroenterol Hepatol"},{"key":"10.1016\/j.ajpath.2021.05.020_bib50","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1073\/pnas.97.2.841","article-title":"Aortic wall damage in mice unable to synthesize ascorbic acid","volume":"97","author":"Maeda","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2021.05.020_bib51","first-page":"956","article-title":"ChREBP, but not LXRs, is required for the induction of glucose-regulated genes in mouse liver","volume":"118","author":"Denechaud","year":"2008","journal-title":"J Clin Invest"}],"container-title":["The American Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944021002558?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944021002558?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T16:38:39Z","timestamp":1757695119000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002944021002558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":51,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["S0002944021002558"],"URL":"https:\/\/doi.org\/10.1016\/j.ajpath.2021.05.020","relation":{},"ISSN":["0002-9440"],"issn-type":[{"value":"0002-9440","type":"print"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Vitamin C Deficiency Inhibits Nonalcoholic Fatty Liver Disease Progression through Impaired de Novo Lipogenesis","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajpath.2021.05.020","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 American Society for Investigative Pathology. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}