Increased liver AGEs induce hepatic injury mediated through an OST48 pathway

Aowen Zhuang; Felicia Y T Yap; Clinton Bruce; Chris Leung; Manuel R Plan; Mitchell A Sullivan; Chandana Herath; Domenica A McCarthy; Karly C Sourris; Phillip Kantharidis; Melinda T Coughlan; Mark A. Febbraio; Mark P Hodson; Matthew J. Watt; Peter Angus; Benjamin L Schulz; Josephine M Forbes

doi:10.1038/s41598-017-12548-4

Back

Increased liver AGEs induce hepatic injury mediated through an OST48 pathway

Journal article

Open access

Peer reviewed

Increased liver AGEs induce hepatic injury mediated through an OST48 pathway

Aowen Zhuang, Felicia Y T Yap, Clinton Bruce, Chris Leung, Manuel R Plan, Mitchell A Sullivan, Chandana Herath, Domenica A McCarthy, Karly C Sourris, Phillip Kantharidis, …

Scientific Reports, Vol.7, pp.1-12

2017

DOI: https://doi.org/10.1038/s41598-017-12548-4

PMID: 28947796

Files and links (1)

pdf

s41598-017-12548-45.73 MBDownload View

Published VersionCC BY V4.0, Open Access

Abstract

hepatocytes

liver fibrosis

The protein oligosaccharyltransferase-48 (OST48) is integral to protein N-glycosylation in the endoplasmic reticulum (ER) but is also postulated to act as a membrane localised clearance receptor for advanced glycation end-products (AGE). Hepatic ER stress and AGE accumulation are each implicated in liver injury. Hence the objective of this study was to increase the expression of OST48 and examine the effects on hepatic function and structure. Groups of 8 week old male mice (n = 10-12/group) over-expressing the gene for OST48, dolichyl-diphosphooligosaccharide- protein glycosyltransferase (DDOST+/-), were followed for 24 weeks, while randomised to diets either low or high in AGE content. By week 24 of the study, either increasing OST48 expression or consumption of high AGE diet impaired liver function and modestly increased hepatic fibrosis, but their combination significantly exacerbated liver injury in the absence of steatosis. DDOST+/- mice had increased both portal delivery and accumulation of hepatic AGEs leading to central adiposity, insulin secretory defects, shifted fuel usage to fatty and ketoacids, as well as hepatic glycogen accumulation causing hepatomegaly along with hepatic ER and oxidative stress. This study revealed a novel role of the OST48 and AGE axis in hepatic injury through ER stress, changes in fuel utilisation and glucose intolerance.

Details

Title: Increased liver AGEs induce hepatic injury mediated through an OST48 pathway
Authors: Aowen Zhuang - The University of Queensland
Felicia Y T Yap - Baker Heart and Diabetes Institute
Clinton Bruce - Deakin University
Chris Leung - The University of Melbourne
Manuel R Plan - The University of Queensland
Mitchell A Sullivan - The University of Queensland
Chandana Herath - The University of Melbourne
Domenica A McCarthy - Translational Research Institute
Karly C Sourris - Monash University
Phillip Kantharidis - Baker Heart and Diabetes Institute
Melinda T Coughlan - Monash University
Mark A. Febbraio - Baker Heart and Diabetes Institute
Mark P Hodson - The University of Queensland
Matthew J. Watt - Monash University
Peter Angus - Austin Hospital
Benjamin L Schulz - The University of Queensland
Josephine M Forbes (Corresponding Author) - The University of Queensland
Publication details: Scientific Reports, Vol.7, pp.1-12
Publisher: Nature Publishing Group
Date published: 2017
DOI: 10.1038/s41598-017-12548-4
ISSN: 2045-2322
PMID: 28947796
Copyright note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Organisation Unit: School of Health - Biomedicine
Language: English
Record Identifier: 991035096702621
Output Type: Journal article

Metrics

9 Record Views

24 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration
Web Of Science research areas: Biochemistry & Molecular Biology

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites