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Metabolic preconditioning of donor organs: Defatting fatty livers by normothermic perfusion ex vivo

Paper ID Volume ID Publish Year Pages File Format Full-Text
31787 44838 2009 10 PDF Available
Title
Metabolic preconditioning of donor organs: Defatting fatty livers by normothermic perfusion ex vivo
Abstract

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 24 h, and of perfused livers by 50% over 3 h. 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.

Keywords
Nuclear receptors; Normothermic perfusion; Hepatocytes; Steatosis; Liver transplantationOLT, Orthotopic liver transplantation; PPARs, Peroxisome proliferators-activated receptors; PXR, Pregnane X receptor (PXR); CAR, Constitutive Androstane Receptor; PBEF
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Metabolic preconditioning of donor organs: Defatting fatty livers by normothermic perfusion ex vivo
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 11, Issues 4–5, July–September 2009, Pages 274–283
Authors
, , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us