Document Detail

Eicosapentaenoic acid improves hepatic steatosis independent of PPARα activation through inhibition of SREBP-1 maturation in mice.
MedLine Citation:
PMID:  20691165     Owner:  NLM     Status:  MEDLINE    
Eicosapentaenoic acid (EPA) in fish oil is known to improve hepatic steatosis. However, it remains unclear whether such action of EPA is actually caused by peroxisome proliferator-activated receptor α (PPARα) activation. To explore the contribution of PPARα to the effects of EPA itself, male wild-type and Ppara-null mice were fed a saturated fat diet for 16 weeks, and highly (>98%)-purified EPA was administered in the last 12 weeks. Furthermore, the changes caused by EPA treatment were compared to those elicited by fenofibrate (FF), a typical PPARα activator. A saturated fat diet caused macrovesicular steatosis in both genotypes. However, EPA ameliorated steatosis only in wild-type mice without PPARα activation, which was evidently different from numerous previous observations. Instead, EPA inhibited maturation of sterol-responsive element-binding protein (SREBP)-1 in the presence of PPARα through down-regulation of SREBP cleavage-activating protein and site-1 protease. Additionally, EPA suppressed fatty acid uptake and promoted hydrolysis of intrahepatic triglycerides in a PPARα-independent manner. These effects were distinct from those of fenofibrate. Although fenofibrate induced NAPDH oxidase and acyl-coenzyme A oxidase and significantly increased hepatic lipid peroxides, EPA caused PPARα-dependent induction of superoxide dismutases, probably contributing to a decrease in the lipid peroxides. These results firstly demonstrate detailed mechanisms of steatosis-ameliorating effects of EPA without PPARα activation and ensuing augmentation of hepatic oxidative stress.
Naoki Tanaka; Xiuguo Zhang; Eiko Sugiyama; Hiroyuki Kono; Akira Horiuchi; Takero Nakajima; Hiroki Kanbe; Eiji Tanaka; Frank J Gonzalez; Toshifumi Aoyama
Related Documents :
3102875 - Asymmetric distribution of arachidonic and n-3 polyunsaturated fatty acids in rat liver...
17069355 - Docosahexaenoic acid levels in the lipids of spotted mackerel scomber australasicus.
10812585 - Triglyceride-lowering effect of omega-3 lc-polyunsaturated fatty acids--a review.
3107535 - Influence of dietary fats on blood coagulation and prostaglandin production in the comm...
8415945 - The effects of cocaine on dietary self-selection in female rats.
7417395 - Biotin status, blood pyruvate carboxylase (ec activity and performance in broi...
Publication Detail:
Type:  Journal Article     Date:  2010-08-04
Journal Detail:
Title:  Biochemical pharmacology     Volume:  80     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-29     Completed Date:  2010-10-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1601-12     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Dietary Fats / administration & dosage,  adverse effects
Disease Models, Animal
Eicosapentaenoic Acid / pharmacology,  therapeutic use*
Fatty Liver / drug therapy*,  etiology,  metabolism,  pathology
Lipid Peroxidation / drug effects
Liver / drug effects,  metabolism,  pathology
Liver Function Tests
Mice, Knockout
Oxidative Stress / drug effects
PPAR alpha / genetics,  metabolism*
Procetofen / pharmacology
Sterol Regulatory Element Binding Protein 1 / antagonists & inhibitors*
Reg. No./Substance:
0/Dietary Fats; 0/PPAR alpha; 0/Srebf1 protein, mouse; 0/Sterol Regulatory Element Binding Protein 1; 1553-41-9/Eicosapentaenoic Acid; 49562-28-9/Procetofen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Chain-dependent photocytotoxicity of tricationic porphyrin conjugates and related mechanisms of cell...
Next Document:  Co-localization of TRHR1 and LepRb receptors on neurons in the hindbrain of the rat.