Dietary glycotoxins exacerbate progression of experimental fatty liver disease

Leung, Christopher, Herath, Chandana B., Jia, Zhiyuan, Goodwin, Michelle, Mak, Kai Yan, Watt, Matthew J., Forbes, Josephine M. and Angus, Peter W. (2014) Dietary glycotoxins exacerbate progression of experimental fatty liver disease. Journal of Hepatology, 60 4: 832-838. doi:10.1016/j.jhep.2013.11.033

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Author Leung, Christopher
Herath, Chandana B.
Jia, Zhiyuan
Goodwin, Michelle
Mak, Kai Yan
Watt, Matthew J.
Forbes, Josephine M.
Angus, Peter W.
Title Dietary glycotoxins exacerbate progression of experimental fatty liver disease
Journal name Journal of Hepatology   Check publisher's open access policy
ISSN 0168-8278
1600-0641
Publication date 2014
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.jhep.2013.11.033
Open Access Status
Volume 60
Issue 4
Start page 832
End page 838
Total pages 7
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2014
Language eng
Formatted abstract
Background & Aims: Advanced glycation end-products (AGEs) levels are high in western diets and contribute to tissue injury via activation of RAGE (receptor for AGEs) and generation of reactive oxygen species (ROS). Here, we determined if high dietary AGE intake worsens progression of non-alcoholic fatty liver disease (NAFLD).

Methods: Male Sprague Dawley rats were fed a methionine choline deficient (MCD) diet for 6 weeks before 6 weeks of a high AGE MCD diet through baking. They were compared with animals on MCD diet or a methionine choline replete (MCR) diet alone for 12 weeks. Hepatic ROS, triglycerides, biochemistry, picro-sirius morphometry, hepatic mRNA expression and immunohistochemistry were determined. Primary hepatic stellate cells (HSCs) from both MCR and MCD animals were exposed to AGEs. ROS, proliferation and mRNA expression were determined.

Results: The high AGE MCD diet increased hepatic AGE content and elevated triglycerides, NADPH dependent superoxide production, HNE adducts, steatosis, steatohepatitis (CD43, IL-6, TNF-α) and fibrosis (α-SMA, CTGF, COL1A, picrosirius) compared to MCD alone. In HSCs, AGEs significantly increased ROS production, bromodeoxyuridine proliferation and MCP-1, IL-6, α-SMA, and RAGE expression in HSCs from MCD but not MCR animals. These effects were abrogated by RAGE or NADPH oxidase blockade.

Conclusions: In the MCD model of NAFLD, high dietary AGEs increases hepatic AGE content and exacerbates liver injury, inflammation, and liver fibrosis via oxidative stress and RAGE dependent profibrotic effects of AGEs on activated HSCs. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.
Keyword Advanced glycation end-products
Hepatic stellate cell
Non-alcoholic fatty liver disease
Oxidative stress
Steatohepatitis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2014 Collection
 
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Created: Thu, 24 Apr 2014, 15:05:14 EST by Dominique Rossouw on behalf of Mater Research Institute-UQ