Nonalcoholic Fatty Liver Disease in Humans Is Associated with Increased Plasma Endotoxin and Plasminogen Activator Inhibitor 1 Concentrations and with Fructose Intake

• Published in: The Journal of nutrition Vol. 138; no. 8; pp. 1452 - 1455
• Main Authors: Thuy, Sabine, Ladurner, Ruth, Volynets, Valentina, Wagner, Silvia, Strahl, Stefan, Königsrainer, Alfred, Maier, Klaus-Peter, Bischoff, Stephan C, Bergheim, Ina
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutrition 01.08.2008; American Society for Nutritional Sciences
• Subjects: administration & dosage; Adult; adverse effects; bacterial overgrowth; Biological and medical sciences; blood; carbohydrate intake; Case-Control Studies; chemically induced; chromosome translocation; Diet; dietary carbohydrate; Dietary Carbohydrates; Dietary Carbohydrates - administration & dosage; Dietary Carbohydrates - adverse effects; Dose-Response Relationship, Drug; drug effects; endotoxins; Endotoxins - blood; fatty liver; Fatty Liver - blood; Fatty Liver - chemically induced; Fatty Liver - metabolism; Feeding. Feeding behavior; Female; fructose; Fructose - administration & dosage; Fructose - adverse effects; Fundamental and applied biological sciences. Psychology; gene expression; Gene Expression Regulation; Gene Expression Regulation - drug effects; genetics; Humans; inhibitors; intestinal microorganisms; Liver; Liver - metabolism; liver function; Male; metabolism; Middle Aged; nutrient intake; nutrition assessment; nutritional status; Pilot Projects; plasma cells; plasminogen activator; Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 1 - blood; Plasminogen Activator Inhibitor 1 - genetics; RNA, Messenger; RNA, Messenger - genetics; RNA, Messenger - metabolism; Toll-Like Receptor 4; Toll-Like Receptor 4 - blood; Toll-Like Receptor 4 - genetics; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; Biological fluid; Toxin; Plasminogen activator inhibitor 1; Nutrition; Non alcoholic steatohepatitis; Digestive diseases; Hepatic disease; Concentration; Endotoxin; Fructose; Blood plasma
• ISSN: 0022-3166; 1541-6100; 1541-6100
• DOI: 10.1093/jn/138.8.1452

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.