Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

Leung, Christopher, Herath, Chandana B., Jia, Zhiyuan, Andrikopoulos, Sof, Brown, Bronwyn E., Davies, Michael J., Rivera, Leni R., Furness, John B., Forbes, Josephine M. and Angus, Peter W. (2016) Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease. World Journal of Gastroenterology, 22 35: 8026-8040. doi:10.3748/wjg.v22.i35.8026

Author Leung, Christopher
Herath, Chandana B.
Jia, Zhiyuan
Andrikopoulos, Sof
Brown, Bronwyn E.
Davies, Michael J.
Rivera, Leni R.
Furness, John B.
Forbes, Josephine M.
Angus, Peter W.
Title Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease
Journal name World Journal of Gastroenterology   Check publisher's open access policy
ISSN 2219-2840
Publication date 2016-09-21
Year available 2016
Sub-type Article (original research)
DOI 10.3748/wjg.v22.i35.8026
Open Access Status Not yet assessed
Volume 22
Issue 35
Start page 8026
End page 8040
Total pages 15
Place of publication Pleasanton, CA, United States
Publisher Baishideng Publishing Group
Language eng
Formatted abstract
Aim: To determine if manipulation of dietary advanced glycation end product (AGE), intake affects nonalcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE.

Methods: Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined.

Results: Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury.

Conclusion: In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.
Keyword Advanced glycation end-products
Non-alcoholic fatty liver disease
Hepatic fibrosis
Oxidative stress
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
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Created: Tue, 15 Nov 2016, 00:31:06 EST by Julia McCabe on behalf of Learning and Research Services (UQ Library)