Document Detail


Mitochondrial dysfunction during in vitro hepatocyte steatosis is reversed by omega-3 fatty acid-induced up-regulation of mitofusin 2.
MedLine Citation:
PMID:  20817187     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We examined the effects and mechanisms of omega-3 polyunsaturated fatty acid (PUFA) administration on mitochondrial morphology and function in an in vitro steatotic hepatocyte model created using HepG2 cells. Reverse transcriptase polymerase chain reaction and Western blot analyses were performed to determine the expression levels of mitofusin 2 (Mfn2), and immunofluorescent MitoTracker Mitochondrion-Selective Probes were used to detect changes in mitochondrial morphology. Adenosine triphosphate (ATP) synthesis and reactive oxygen species (ROS) production were measured to assess mitochondrial function. Mitofusin 2 expression was significantly suppressed (P < .05), ATP levels were decreased (P < .05), ROS production was increased (P < .05), and the normal tubular network of mitochondria was fragmented into short rods or spheres. Model cells were incubated with eicosapentaenoic acid or docosahexaenoic acid at a final concentration of 50 μmol/L for 1 hour. Both eicosapentaenoic acid and docosahexaenoic acid increased the expression of Mfn2 (P < .01) and caused an increase in the length of mitochondrial tubules. The omega-3 PUFAs also increased the levels of ATP (P < .05) and decreased the ROS production (P < .05). However, these changes were not seen in Mfn2-depleted steatotic HepG2 cells, created by RNA interference before incubation with the omega-3 PUFAs. This study demonstrated that, in steatotic hepatocytes, omega-3 PUFAs may change mitochondrial morphology and have beneficial effects on recovery of mitochondrial function by increasing the expression of Mfn2.
Authors:
Yong Zhang; Longchang Jiang; Wenjun Hu; Qichang Zheng; Wenpei Xiang
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Publication Detail:
Type:  Journal Article     Date:  2010-09-03
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  60     ISSN:  1532-8600     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-17     Completed Date:  2011-07-19     Revised Date:  2011-12-19    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  United States    
Other Details:
Languages:  eng     Pagination:  767-75     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of General Surgery, Union Hospital, Huazhong University of Science and Technology, China, 430022.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Azo Compounds
Blotting, Western
Cells, Cultured
Coloring Agents
Fatty Acids, Omega-3 / therapeutic use*
Fatty Liver / drug therapy*,  pathology*
Fluorometry
Hepatocytes / drug effects,  metabolism,  pathology*
Humans
Image Processing, Computer-Assisted
Membrane Proteins / biosynthesis*
Microscopy, Fluorescence
Mitochondria, Liver / drug effects,  pathology*,  ultrastructure
Mitochondrial Proteins / biosynthesis*
RNA, Messenger / biosynthesis,  genetics
RNA, Small Interfering / pharmacology
Reactive Oxygen Species / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Up-Regulation / drug effects
Chemical
Reg. No./Substance:
0/Azo Compounds; 0/Coloring Agents; 0/Fatty Acids, Omega-3; 0/Membrane Proteins; 0/Mitochondrial Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Reactive Oxygen Species; 1320-06-5/oil red O; 56-65-5/Adenosine Triphosphate; EC 3.6.1.-/MFN2 protein, human

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


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