title: Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake.
abstract: Results of animal experiments suggest that consumption of refined carbohydrates (e.g. fructose) can result in small intestinal bacterial overgrowth and increased intestinal permeability, thereby contributing to the development of nonalcoholic fatty liver disease (NAFLD). Furthermore, increased plasminogen activator inhibitor (PAI)-1 has been linked to liver damage of various etiologies (e.g. alcohol, endotoxin, nonalcoholic). The aim of the present pilot study was to compare dietary factors, endotoxin, and PAI-1 concentrations between NAFLD patients and controls. We assessed the dietary intake of 12 patients with NAFLD and 6 control subjects. Plasma endotoxin and PAI-1 concentrations as well as hepatic expression of PAI-1 and toll-like receptor (TLR) 4 mRNA were determined. Despite similar total energy, fat, protein, and carbohydrate intakes, patients with NAFLD consumed significantly more fructose than controls. Endotoxin and PAI-1 plasma concentrations as well as hepatic TLR4 and PAI-1 mRNA expression of NAFLD patients were significantly higher than in controls. The plasma PAI-1 concentration was positively correlated with the plasma endotoxin concentration (Spearman r = 0.83; P < 0.005) and hepatic TLR4 mRNA expression (Spearman r = 0.54; P < 0.05). Hepatic mRNA expression of PAI-1 was positively associated with dietary intakes of carbohydrates (Spearman r = 0.67; P < 0.01), glucose (Spearman r = 0.58; P < 0.01), fructose (Spearman r = 0.58; P < 0.01), and sucrose (Spearman r = 0.70; P < 0.01). In conclusion, our results suggest that dietary fructose intake, increased intestinal translocation of bacterial endotoxin, and PAI-1 may contribute to the development of NAFLD in humans.
authors.affiliation: Department of Nutritional Medicine (180a), University of Hohenheim, 70599 Stuttgart, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Thuy
authors.forename: Ruth
authors.initials: R
authors.lastname: Ladurner
authors.forename: Valentina
authors.initials: V
authors.lastname: Volynets
authors.forename: Silvia
authors.initials: S
authors.lastname: Wagner
authors.forename: Stefan
authors.initials: S
authors.lastname: Strahl
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Maier
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Bischoff
authors.forename: Ina
authors.initials: I
authors.lastname: Bergheim
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000097:blood*; D005234:Fatty Liver / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000097:blood / Q000235:genetics
chemical_list: D004040:Dietary Carbohydrates; D004731:Endotoxins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D005632:Fructose