{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:39:16Z","timestamp":1792003156289,"version":"4.4.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T00:00:00Z","timestamp":1559260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T00:00:00Z","timestamp":1559260800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:p>Fructose intake is known to induce obesity, insulin resistance, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the effects of fructose drinking on gut leakiness, endotoxemia, and NAFLD and study the underlying mechanisms in rats, mice, and T84 colon cells. Levels of ileum junctional proteins, oxidative stress markers, and apoptosis\u2010related proteins in rodents, T84 colonic cells, and human ileums were determined by immunoblotting, immunoprecipitation, and immunofluorescence analyses. Fructose drinking caused microbiome change, leaky gut, and hepatic inflammation\/fibrosis with increased levels of nitroxidative stress marker proteins cytochrome P450\u20102E1 (CYP2E1), inducible nitric oxide synthase, and nitrated proteins in small intestine and liver of rodents. Fructose drinking significantly elevated plasma bacterial endotoxin levels, likely resulting from decreased levels of intestinal tight junction (TJ) proteins (zonula occludens 1, occludin, claudin\u20101, and claudin\u20104), adherent junction (AJ) proteins (\u03b2\u2010catenin and E\u2010cadherin), and desmosome plakoglobin, along with \u03b1\u2010tubulin, in wild\u2010type rodents, but not in fructose\u2010exposed <jats:italic toggle=\"yes\">Cyp2e1<\/jats:italic>\u2010null mice. Consistently, decreased intestinal TJ\/AJ proteins and increased hepatic inflammation with fibrosis were observed in autopsied obese people compared to lean individuals. Furthermore, histological and biochemical analyses showed markedly elevated hepatic fibrosis marker proteins in fructose\u2010exposed rats compared to controls. Immunoprecipitation followed by immunoblot analyses revealed that intestinal TJ proteins were nitrated and ubiquitinated, leading to their decreased levels in fructose\u2010exposed rats. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> These results showed that fructose intake causes protein nitration of intestinal TJ and AJ proteins, resulting in increased gut leakiness, endotoxemia, and steatohepatitis with liver fibrosis, at least partly, through a CYP2E1\u2010dependent manner.<\/jats:p>","DOI":"10.1002\/hep.30652","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T19:40:10Z","timestamp":1554752410000},"page":"2180-2195","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":226,"title":["Fructose Promotes Leaky Gut, Endotoxemia, and Liver Fibrosis Through Ethanol\u2010Inducible Cytochrome P450\u20102E1\u2013Mediated Oxidative and Nitrative Stress"],"prefix":"10.1097","volume":"73","author":[{"given":"Young\u2010Eun","family":"Cho","sequence":"first","affiliation":[{"name":"Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics,National Institute on Alcohol Abuse and Alcoholism, NIH,Bethesda,MD"},{"name":"Department of Food and Nutrition,Andong National University,Andong,South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do\u2010Kyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Mast Cell Biology Section, Laboratory of Allergic Diseases,National Institute of Allergy and Infectious Diseases, National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonhyo","family":"Seo","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong\u2010Ho","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine,Seoul National University College of Medicine,Seoul,South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung\u2010Joon","family":"Song","sequence":"additional","affiliation":[{"name":"Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics,National Institute on Alcohol Abuse and Alcoholism, 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