| Metabolic preconditioning of donor organs: defatting fatty livers by normothermic perfusion ex vivo. | |
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MedLine Citation:
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PMID: 19508897 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Deepak Nagrath; Hongzhi Xu; Yoko Tanimura; Rongjun Zuo; François Berthiaume; Marco Avila; Rubin Yarmush; Martin L Yarmush |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-06-07 |
Journal Detail:
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Title: Metabolic engineering Volume: 11 ISSN: 1096-7184 ISO Abbreviation: Metab. Eng. Publication Date: 2009 Jul-Sep |
Date Detail:
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Created Date: 2009-08-11 Completed Date: 2009-11-13 Revised Date: 2011-10-31 |
Medline Journal Info:
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Nlm Unique ID: 9815657 Medline TA: Metab Eng Country: Belgium |
Other Details:
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Languages: eng Pagination: 274-83 Citation Subset: IM |
Affiliation:
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Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and the Shriners Hospitals for Children, Boston, MA 02114, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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P30 DK040561-14/DK/NIDDK NIH HHS; P41EB002503/EB/NIBIB NIH HHS; R01 DK059766-05A2/DK/NIDDK NIH HHS; R01DK059766/DK/NIDDK NIH HHS; R01DK43371/DK/NIDDK NIH HHS |
| Comments/Corrections | |
Comment In:
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Liver Transpl. 2009 Oct;15(10):1366-7
[PMID:
19806685
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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