Background/Aims
While the rise in non-alcoholic fatty liver disease (NAFLD) parallels the increase
in obesity and diabetes, a significant increase in dietary fructose consumption in
industrialized countries has also occurred. The increased consumption of high fructose
corn syrup, primarily in the form of soft drinks, is linked with complications of
the insulin resistance syndrome. Furthermore, the hepatic metabolism of fructose favors
de novo lipogenesis and ATP depletion. We hypothesize that increased fructose consumption
contributes to the development of NAFLD.
Methods
A dietary history and paired serum and liver tissue were obtained from patients with
evidence of biopsy-proven NAFLD (n = 49) without cirrhosis and controls (n = 24) matched for gender, age (±5 years), and body mass index (±3 points).
Results
Consumption of fructose in patients with NAFLD was nearly 2- to 3-fold higher than
controls [365 kcal vs 170 kcal (p < 0.05)]. In patients with NAFLD (n = 6), hepatic mRNA expression of fructokinase (KHK), an important enzyme for fructose
metabolism, and fatty acid synthase, an important enzyme for lipogenesis were increased
(p = 0.04 and p = 0.02, respectively). In an AML hepatocyte cell line, fructose resulted in dose-dependent
increase in KHK protein and activity.
Conclusions
The pathogenic mechanism underlying the development of NAFLD may be associated with
excessive dietary fructose consumption.
Abbreviations:
NAFLD (non-alcoholic fatty liver disease), KHK (hexokinase), FAS (fatty acid synthase), XDH (xanthine dehydrogenase)Keywords
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Article info
Publication history
Published online: March 10, 2008
Accepted:
February 1,
2008
Received in revised form:
February 1,
2008
Received:
December 18,
2007
Associate Editor: C.P. DayFootnotes
☆R.J. Johnson and Y. Sautin are listed as inventors on patent applications by the University of Florida related to the role of fructose in hypertension and metabolic syndrome. Dr. Johnson has also written a book on fructose for the lay public (Rodale Press, 2008). NIH funded study (Grants DK-52121, HL-68607, DK-79352 and K23 DK062116).
Identification
Copyright
© 2008 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
