Insulin Resistance, Ceramide Accumulation, and Endoplasmic Reticulum Stress in Human Chronic Alcohol-Related Liver Disease
Joint Authors
de la Monte, Suzanne M.
Longato, Lisa
Branda, Mark
Ripp, Kelsey
Dostalek, Miroslav
Akhlaghi, Fatemeh
Wands, Jack R.
Setshedi, Mashiko
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-04-22
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
Background.
Chronic alcohol-related liver disease (ALD) is mediated by insulin resistance, mitochondrial dysfunction, inflammation, oxidative stress, and DNA damage.
Recent studies suggest that dysregulated lipid metabolism with accumulation of ceramides, together with ER stress potentiate hepatic insulin resistance and may cause steatohepatitis to progress.
Objective.
We examined the degree to which hepatic insulin resistance in advanced human ALD is correlated with ER stress, dysregulated lipid metabolism, and ceramide accumulation.
Methods.
We assessed the integrity of insulin signaling through the Akt pathway and measured proceramide and ER stress gene expression, ER stress signaling proteins, and ceramide profiles in liver tissue.
Results.
Chronic ALD was associated with increased expression of insulin, IGF-1, and IGF-2 receptors, impaired signaling through IGF-1R and IRS1, increased expression of multiple proceramide and ER stress genes and proteins, and higher levels of the C14, C16, C18, and C20 ceramide species relative to control.
Conclusions.
In human chronic ALD, persistent hepatic insulin resistance is associated with dysregulated lipid metabolism, ceramide accumulation, and striking upregulation of multiple ER stress signaling molecules.
Given the role of ceramides as mediators of ER stress and insulin resistance, treatment with ceramide enzyme inhibitors may help reverse or halt progression of chronic ALD.
American Psychological Association (APA)
Longato, Lisa& Ripp, Kelsey& Setshedi, Mashiko& Dostalek, Miroslav& Akhlaghi, Fatemeh& Branda, Mark…[et al.]. 2012. Insulin Resistance, Ceramide Accumulation, and Endoplasmic Reticulum Stress in Human Chronic Alcohol-Related Liver Disease. Oxidative Medicine and Cellular Longevity،Vol. 2012, no. 2012, pp.1-17.
https://search.emarefa.net/detail/BIM-474806
Modern Language Association (MLA)
Longato, Lisa…[et al.]. Insulin Resistance, Ceramide Accumulation, and Endoplasmic Reticulum Stress in Human Chronic Alcohol-Related Liver Disease. Oxidative Medicine and Cellular Longevity No. 2012 (2012), pp.1-17.
https://search.emarefa.net/detail/BIM-474806
American Medical Association (AMA)
Longato, Lisa& Ripp, Kelsey& Setshedi, Mashiko& Dostalek, Miroslav& Akhlaghi, Fatemeh& Branda, Mark…[et al.]. Insulin Resistance, Ceramide Accumulation, and Endoplasmic Reticulum Stress in Human Chronic Alcohol-Related Liver Disease. Oxidative Medicine and Cellular Longevity. 2012. Vol. 2012, no. 2012, pp.1-17.
https://search.emarefa.net/detail/BIM-474806
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-474806