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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ishimoto, T; Lanaspa, MA; Rivard, CJ; Roncal-Jimenez, CA; Orlicky, DJ; Cicerchi, C; Mcmahan, RH; Abdelmalek, MF; Rosen, HR; Jackman, MR; Maclean, PS; Diggle, CP; Asipu, A; Inaba, S; Kosugi, T; Sato, W; Maruyama, S; Sánchez-Lozada, LG; Sautin, YY; Hill, JO; Bonthron, DT; Johnson, RJ

Published Date

  • November 1, 2013

Published In

Volume / Issue

  • 58 / 5

Start / End Page

  • 1632 - 1643

Electronic International Standard Serial Number (EISSN)

  • 1527-3350

International Standard Serial Number (ISSN)

  • 0270-9139

Digital Object Identifier (DOI)

  • 10.1002/hep.26594

Citation Source

  • Scopus