Document Detail


Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease.
MedLine Citation:
PMID:  23178552     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The steady rise in Western obesity rates has been closely linked to significant increases in a multitude of accompanying health problems including non-alcoholic fatty liver disease (NAFLD). NAFLD severity ranges from simple steatosis to acute steatohepatitis, but the molecular mechanisms controlling progression of this disease are poorly understood. Recent literature suggests that elevated free fatty acids (FFAs), especially saturated FFAs, may play an important role in lipotoxic mechanisms, both in experimental models and in NAFLD patients. This review highlights important cellular pathways involved in hepatic lipotoxicity and how the degree of intrahepatic lipid saturation controls cell fate in response to an elevated FFA load. Relevant cellular processes that have been causally linked to lipid-induced apoptosis, known as lipoapoptosis, include endoplasmic reticulum (ER) stress, oxidative stress, mitochondrial dysfunction, and Jun N-terminal kinase (JNK) signaling. In contrast, increased triglyceride synthesis has been shown to have a protective effect against lipotoxicity, despite being one of the hallmark traits of NAFLD. Developing a more nuanced understanding of the molecular mechanisms underlying NAFLD progression will lead to more targeted and effective therapeutics for this increasingly prevalent disease, which to date has no proven pharmacologic treatment to prevent or reverse its course.
Authors:
Alexandra K Leamy; Robert A Egnatchik; Jamey D Young
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Review     Date:  2012-11-23
Journal Detail:
Title:  Progress in lipid research     Volume:  52     ISSN:  1873-2194     ISO Abbreviation:  Prog. Lipid Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-07-12     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  7900832     Medline TA:  Prog Lipid Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  165-74     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Clinical Trials as Topic
Disease Progression
Endoplasmic Reticulum / metabolism
Fatty Acids / metabolism*
Fatty Liver / metabolism*,  therapy
Humans
Mitochondria / metabolism
Oxidative Stress
Reactive Oxygen Species / metabolism
Triglycerides / metabolism
Grant Support
ID/Acronym/Agency:
DK020593/DK/NIDDK NIH HHS; P60 DK020593/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Reactive Oxygen Species; 0/Triglycerides
Comments/Corrections

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