Document Detail


Metabolic preconditioning of donor organs: defatting fatty livers by normothermic perfusion ex vivo.
MedLine Citation:
PMID:  19508897     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fatty liver is a significant risk factor for liver transplantation, and accounts for nearly half of the livers rejected from the donor pool. We hypothesized that metabolic preconditioning via ex vivo perfusion of the liver graft can reduce fat content and increase post-transplant survival to an acceptable range. We describe a perfusate medium containing agents that promote the defatting of hepatocytes and explanted livers. Defatting agents were screened on cultured hepatocytes made fatty by pre-incubation with fatty acids. The most effective agents were then used on fatty livers. Fatty livers were isolated from obese Zucker rats and normothermically perfused with medium containing a combination of defatting agents. This combination decreased the intracellular lipid content of cultured hepatocytes by 35% over 24h, and of perfused livers by 50% over 3h. Metabolite analysis suggests that the defatting cocktail upregulated both lipid oxidation and export. Furthermore, gene expression analysis for several enzymes and transcription factors involved in fatty acid oxidation and triglyceride clearance were elevated. We conclude that a cocktail of defatting agents can be used to rapidly clear excess lipid storage in fatty livers, thus providing a new means to recondition donor livers deemed unacceptable or marginally acceptable for transplantation.
Authors:
Deepak Nagrath; Hongzhi Xu; Yoko Tanimura; Rongjun Zuo; François Berthiaume; Marco Avila; Rubin Yarmush; Martin L Yarmush
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-06-07
Journal Detail:
Title:  Metabolic engineering     Volume:  11     ISSN:  1096-7184     ISO Abbreviation:  Metab. Eng.     Publication Date:    2009 Jul-Sep
Date Detail:
Created Date:  2009-08-11     Completed Date:  2009-11-13     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  9815657     Medline TA:  Metab Eng     Country:  Belgium    
Other Details:
Languages:  eng     Pagination:  274-83     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Culture Techniques
Cell Survival
Cells, Cultured
Fatty Liver / metabolism*
Female
Hepatocytes / cytology
Heterozygote
Homozygote
Humans
Liver Transplantation*
Perfusion / methods*
Rats
Rats, Inbred Lew
Rats, Zucker
Survival Analysis
Time Factors
Tissue Donors*
Grant Support
ID/Acronym/Agency:
P30 DK040561/DK/NIDDK NIH HHS; P30 DK040561-14/DK/NIDDK NIH HHS; P41EB002503/EB/NIBIB NIH HHS; R01 DK059766/DK/NIDDK NIH HHS; R01 DK059766-05A2/DK/NIDDK NIH HHS; R01DK059766/DK/NIDDK NIH HHS; R01DK43371/DK/NIDDK NIH HHS
Comments/Corrections
Comment In:
Liver Transpl. 2009 Oct;15(10):1366-7   [PMID:  19806685 ]

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


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