{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T21:21:02Z","timestamp":1780521662432,"version":"3.54.1"},"reference-count":114,"publisher":"Canadian Science Publishing","issue":"10","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p> Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD. <\/jats:p>","DOI":"10.1139\/cjpp-2016-0681","type":"journal-article","created":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T21:36:48Z","timestamp":1493674608000},"page":"1141-1148","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":75,"title":["Role of folate in nonalcoholic fatty liver disease"],"prefix":"10.1139","volume":"95","author":[{"given":"Victoria","family":"Sid","sequence":"first","affiliation":[{"name":"St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada."},{"name":"Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaw L.","family":"Siow","sequence":"additional","affiliation":[{"name":"St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada."},{"name":"Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada."},{"name":"Agriculture and Agri-Food Canada, Winnipeg, MB R3C 1B2, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karmin","family":"O","sequence":"additional","affiliation":[{"name":"St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada."},{"name":"Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada."},{"name":"Department of Animal Science, University of Manitoba, Winnipeg, MB R3T 2N2, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-0125-z"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v7.i11.1450"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.03.019"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1139\/Y05-136"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.28427"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902072106"},{"issue":"2","key":"refg7\/ref7","first-page":"171","volume":"1","author":"Barlowe C.K.","year":"1988","journal-title":"Biofactors"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.3945\/jn.114.199117"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26672"},{"key":"refg10\/ref10","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1986"},{"issue":"13","key":"refg11\/ref11","first-page":"1049","volume":"274","author":"Boushey C.J.","year":"1995","journal-title":"Probable benefits of increasing folic acid intakes. JAMA"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.23.2520"},{"key":"refg13\/ref13","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i42.5286"},{"key":"refg14\/ref14","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22779"},{"key":"refg15\/ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2015.12.012"},{"key":"refg16\/ref16","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v110.pm8613033"},{"key":"refg17\/ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.01.007"},{"issue":"31","key":"refg18\/ref18","first-page":"980","volume":"59","author":"CDC","year":"2010","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"refg19\/ref19","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25762"},{"key":"refg20\/ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2011.12.012"},{"issue":"9","key":"refg21\/ref21","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1093\/jn\/137.9.2036","volume":"137","author":"Chou Y.F.","year":"2007","journal-title":"J. Nutr."},{"key":"refg22\/ref22","doi-asserted-by":"publisher","DOI":"10.3945\/jn.110.124917"},{"key":"refg23\/ref23","first-page":"S59","volume":"52","author":"Clarke R.","year":"2000","journal-title":"Indian Heart J."},{"key":"refg24\/ref24","doi-asserted-by":"publisher","DOI":"10.1126\/science.1204265"},{"key":"refg25\/ref25","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1154"},{"key":"refg26\/ref26","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.11.017"},{"key":"refg27\/ref27","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70599-2"},{"key":"refg28\/ref28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067103"},{"key":"refg29\/ref29","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejcn.1602897"},{"key":"refg30\/ref30","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23621"},{"key":"refg31\/ref31","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21802"},{"key":"refg32\/ref32","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.11.038"},{"key":"refg33\/ref33","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23280"},{"key":"refg34\/ref34","doi-asserted-by":"publisher","DOI":"10.1038\/nature13236"},{"key":"refg35\/ref35","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20973"},{"key":"refg36\/ref36","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(95)00116-T"},{"key":"refg37\/ref37","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejcn.1602212"},{"key":"refg38\/ref38","doi-asserted-by":"publisher","DOI":"10.1021\/jf070986x"},{"key":"refg39\/ref39","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705776"},{"key":"refg40\/ref40","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3311"},{"key":"refg41\/ref41","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.110.035006"},{"key":"refg42\/ref42","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(97)00097-X"},{"key":"refg43\/ref43","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205000200"},{"key":"refg44\/ref44","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2004.03.022"},{"key":"refg45\/ref45","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.16.2015"},{"issue":"1","key":"refg46\/ref46","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1093\/ajcn\/58.1.80","volume":"58","author":"Horne D.W.","year":"1993","journal-title":"Am. J. Clin. Nutr."},{"key":"refg47\/ref47","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2013.807221"},{"issue":"1","key":"refg48\/ref48","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/jn\/131.1.33","volume":"131","author":"Huang R.F.","year":"2001","journal-title":"J. Nutr."},{"key":"refg49\/ref49","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00272.2010"},{"key":"refg51\/ref51","unstructured":"Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. 1998. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. The National Academies Press, Washington, D.C."},{"key":"refg52\/ref52","doi-asserted-by":"publisher","DOI":"10.2174\/1568010033484106"},{"key":"refg53\/ref53","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3841.2009.01359.x"},{"key":"refg54\/ref54","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00543-3"},{"key":"refg55\/ref55","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00285"},{"issue":"11","key":"refg56\/ref56","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1093\/jn\/124.11.2197","volume":"124","author":"Kim Y.I.","year":"1994","journal-title":"J. Nutr."},{"key":"refg57\/ref57","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701"},{"issue":"3","key":"refg58\/ref58","first-page":"351","volume":"20","author":"Kohjima M.","year":"2007","journal-title":"Int. J. Mol. Med."},{"key":"refg59\/ref59","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2012.11.012"},{"key":"refg60\/ref60","doi-asserted-by":"publisher","DOI":"10.3181\/0902-RM-44"},{"key":"refg61\/ref61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2008.05543.x"},{"key":"refg62\/ref62","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R700019-JLR200"},{"key":"refg63\/ref63","doi-asserted-by":"publisher","DOI":"10.1016\/S1590-8658(04)00094-5"},{"key":"refg64\/ref64","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060900"},{"key":"refg65\/ref65","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2000.3027"},{"key":"refg66\/ref66","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejcn.1602771"},{"key":"refg67\/ref67","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.8.1844"},{"key":"refg68\/ref68","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2011.04.002"},{"key":"refg69\/ref69","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114507798999"},{"key":"refg70\/ref70","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201200077"},{"key":"refg71\/ref71","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21224"},{"key":"refg72\/ref72","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-004-2253-z"},{"key":"refg73\/ref73","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2008.08.001"},{"key":"refg74\/ref74","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3204"},{"key":"refg75\/ref75","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301982200"},{"key":"refg76\/ref76","doi-asserted-by":"publisher","DOI":"10.1177\/1535370215579161"},{"key":"refg77\/ref77","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1971.tb02704.x"},{"key":"refg78\/ref78","doi-asserted-by":"publisher","DOI":"10.2165\/11532990-000000000-00000"},{"key":"refg79\/ref79","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.079855"},{"key":"refg80\/ref80","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2011.11.026"},{"key":"refg81\/ref81","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.09.041"},{"key":"refg82\/ref82","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2008.11.005"},{"key":"refg83\/ref83","doi-asserted-by":"publisher","DOI":"10.1007\/s002800050636"},{"key":"refg84\/ref84","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.10.003"},{"issue":"12","key":"refg85\/ref85","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1093\/jn\/121.12.1955","volume":"121","author":"Rong N.","year":"1991","journal-title":"J. Nutr."},{"key":"refg86\/ref86","doi-asserted-by":"publisher","DOI":"10.1038\/414799a"},{"key":"refg87\/ref87","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.23256"},{"key":"refg88\/ref88","doi-asserted-by":"publisher","DOI":"10.1139\/y11-124"},{"key":"refg89\/ref89","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-8777(99)00027-0"},{"key":"refg90\/ref90","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12212"},{"key":"refg91\/ref91","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M200488-JLR200"},{"key":"refg92\/ref92","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(02)00073-9"},{"issue":"5","key":"refg93\/ref93","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1093\/jn\/137.5.1149","volume":"137","author":"Shafizadeh T.B.","year":"2007","journal-title":"J. Nutr."},{"key":"refg94\/ref94","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(76)90326-3"},{"key":"refg95\/ref95","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00260.2015"},{"key":"refg96\/ref96","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0803265"},{"key":"refg97\/ref97","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109467"},{"key":"refg98\/ref98","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2004.tb00070.x"},{"key":"refg99\/ref99","doi-asserted-by":"publisher","DOI":"10.3945\/an.111.000596"},{"key":"refg100\/ref100","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26749"},{"key":"refg101\/ref101","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i19.2300"},{"key":"refg102\/ref102","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.012809.104810"},{"key":"refg103\/ref103","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24001"},{"issue":"2","key":"refg104\/ref104","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0002-8223(21)04765-9","volume":"78","author":"Updegraff T.A.","year":"1981","journal-title":"J. Am. Diet. Assoc."},{"key":"refg105\/ref105","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0587"},{"key":"refg106\/ref106","doi-asserted-by":"publisher","DOI":"10.1042\/CS20030285"},{"key":"refg107\/ref107","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20781"},{"key":"refg108\/ref108","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020911-153251"},{"key":"refg109\/ref109","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.325.7374.1202"},{"key":"refg110\/ref110","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.10.033"},{"key":"refg112\/ref112","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.05.012"},{"key":"refg113\/ref113","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114507777140"},{"key":"refg114\/ref114","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399409000969"},{"key":"refg115\/ref115","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-072610-145133"},{"key":"refg116\/ref116","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.188672"}],"container-title":["Canadian Journal of Physiology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdnsciencepub.com\/doi\/full-xml\/10.1139\/cjpp-2016-0681","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdnsciencepub.com\/doi\/pdf\/10.1139\/cjpp-2016-0681","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T17:32:49Z","timestamp":1751477569000},"score":1,"resource":{"primary":{"URL":"https:\/\/cdnsciencepub.com\/doi\/10.1139\/cjpp-2016-0681"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10]]},"references-count":114,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1139\/cjpp-2016-0681"],"URL":"https:\/\/doi.org\/10.1139\/cjpp-2016-0681","relation":{},"ISSN":["0008-4212","1205-7541"],"issn-type":[{"value":"0008-4212","type":"print"},{"value":"1205-7541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10]]},"assertion":[{"value":"2016-11-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-05-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}