| A New Model of Interactive Effects of Alcohol and High-Fat Diet on Hepatic Fibrosis. | |
| | |
MedLine Citation:
|
PMID: 21463337 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Background: Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are the most frequent conditions leading to elevated liver enzymes and liver cirrhosis, respectively, in the Western world. However, despite strong epidemiological evidence for combined effects on the progression of liver injury, the mutual interaction of the pathophysiological mechanisms is incompletely understood. The aim of this study was to establish and analyze an experimental murine model, where we combined chronic alcohol administration with a NASH-inducing high-fat (HF) diet. Methods: Balb/c mice were randomly allocated into 4 experimental groups receiving (i) standard chow, (ii) an HF diet, (iii) alcohol in drinking water (increasing concentrations up to 5%), or (iv) an HF diet and alcohol ad libitum for 6 weeks. Results: An HF diet significantly induced hepatic triglyceride accumulation and expression of proinflammatory genes (p47(phox) and tumor necrosis factor), while the effects of alcohol alone were less pronounced. However, in combination with HF diet, alcohol significantly enhanced proinflammatory gene expression compared to the HF diet alone. Furthermore, alcohol as well as HF diet led to a marked increase in profibrogenic genes (collagen type I and transforming growth factor-β), activation of hepatic stellate cells, and extracellular matrix deposition in the liver tissue, and noteworthy, the combination of both alcohol and HF diet led to a further marked induction of hepatic fibrosis. Moreover, endotoxin levels in the portal circulation were significantly elevated in mice that received alcohol or HF diet and were further significantly increased in those receiving both. Furthermore and surprisingly, HF diet alone and in combination with alcohol led to a markedly increased hepatic expression of the endotoxin receptor Toll-like receptor 4 (TLR4), which is known to play a crucial role in hepatic fibrosis. Conclusions: In summary, this new model allows the investigation of isolated or joint effects of alcohol and HF diet on hepatic injury, where alcohol and HF diet appear to act synergistically on the development of hepatic fibrosis, potentially via enhanced TLR4 signaling. |
| | |
Authors:
|
Erwin Gäbele; Karin Dostert; Christoph Dorn; Eleonora Patsenker; Felix Stickel; Claus Hellerbrand |
Related Documents
:
|
15052597 - Seasonal variation in body mass and locomotor kinetics of the fat-tailed dwarf lemur (c... 9130027 - Reproducibility of anthropometric and body composition measurements: the heritage famil... 17299077 - Relationship of obesity with osteoporosis. 17679047 - Validation of a three-frequency bioimpedance spectroscopic method for body composition ... 2722707 - Modulation of luteal activity in postpartum beef cows through changes in dietary lipid. 8089727 - Dietary niacin deficiency lowers tissue poly(adp-ribose) and nad+ concentrations in fis... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-4-4 |
Journal Detail:
|
Title: Alcoholism, clinical and experimental research Volume: - ISSN: 1530-0277 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
|
Created Date: 2011-4-5 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7707242 Medline TA: Alcohol Clin Exp Res Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 by the Research Society on Alcoholism. |
Affiliation:
|
From the Department of Internal Medicine I (EG, KD, CD, CH), University Medical Centre Regensburg, Regensburg, Germany; and the Department of Visceral Surgery and Medicine (EP, FS), Inselspital, University of Bern, Bern, Switzerland. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A Longitudinal Twin Study of Effects of Adolescent Alcohol Abuse on the Neurophysiology of Attention...
Next Document: Ethanol Inhibits Lipid Raft-Mediated TCR Signaling and IL-2 Expression: Potential Mechanism of Alcoh...