High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase

Academic Article

Abstract

  • Fructose intake from added sugars has been implicated as a cause of nonalcoholic fatty liver disease. Here we tested the hypothesis that fructose may interact with a high-fat diet to induce fatty liver, and to determine if this was dependent on a key enzyme in fructose metabolism, fructokinase. Wild-type or fructokinase knockout mice were fed a low-fat (11%), high-fat (36%), or high-fat (36%) and high-sucrose (30%) diet for 15 weeks. Both wild-type and fructokinase knockout mice developed obesity with mild hepatic steatosis and no evidence of hepatic inflammation on a high-fat diet compared to a low-fat diet. In contrast, wild-type mice fed a high-fat and high-sucrose diet developed more severe hepatic steatosis with low-grade inflammation and fibrosis, as noted by increased CD68, tumor necrosis factor alpha, monocyte chemoattractant protein-1, alpha-smooth muscle actin, and collagen I and TIMP1 expression. These changes were prevented in the fructokinase knockout mice. Conclusion: An additive effect of high-fat and high-sucrose diet on the development of hepatic steatosis exists. Further, the combination of sucrose with high-fat diet may induce steatohepatitis. The protection in fructokinase knockout mice suggests a key role for fructose (from sucrose) in this development of steatohepatitis. These studies emphasize the important role of fructose in the development of fatty liver and nonalcoholic steatohepatitis. © 2013 by the American Association for the Study of Liver Diseases.
  • Authors

    Published In

  • Hepatology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Ishimoto T; Lanaspa MA; Rivard CJ; Roncal-Jimenez CA; Orlicky DJ; Cicerchi C; Mcmahan RH; Abdelmalek MF; Rosen HR; Jackman MR
  • Start Page

  • 1632
  • End Page

  • 1643
  • Volume

  • 58
  • Issue

  • 5