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

Abstract

UNLABELLED:

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.

• Authors: Takuji Ishimoto, Miguel A Lanaspa, Christopher J Rivard, Carlos A Roncal-Jimenez, David J Orlicky, Christina Cicerchi, Rachel H McMahan, Manal F Abdelmalek, Hugo R Rosen, Matthew R Jackman, Paul S MacLean, Christine P Diggle, Aruna Asipu, Shinichiro Inaba, Tomoki Kosugi, Waichi Sato, Shoichi Maruyama, Laura G Sánchez-Lozada, Yuri Y Sautin, James O Hill, David T Bonthron, Richard J Johnson
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 58 Issue 5 Pg. 1632-43 (Nov 2013) ISSN: 1527-3350 [Electronic] United States
• PMID: 23813872 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 by the American Association for the Study of Liver Diseases.

Chemical References

• Fructose
• Sucrose
• Fructokinases
• fructokinase

Topics

• Animals
• Diet, High-Fat
• Energy Intake
• Fatty Liver (etiology)
• Fructokinases (physiology)
• Fructose (metabolism)
• Liver (metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Sucrose (administration & dosage)
• Weight Gain