Fatty acid synthase blockade protects steatotic livers from warm ischemia reperfusion injury and transplantation

被引：46

作者：

Chavin, KD ^{[1
]}

Fiorini, RN

Shafizadeh, S

Cheng, G

Wan, CD

Evans, Z

Rodwell, D

Polito, C

Haines, JK

Baillie, GM

Schmidt, MG

机构：

[1] Med Univ S Carolina, Dept Surg, Div Transplant, Charleston, SC 29425 USA

[2] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA

[3] Med Univ S Carolina, Dept Pharm Serv, Charleston, SC 29425 USA

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2004年 / 4卷 / 09期

关键词：

liver; steatosis; transplant;

D O I：

10.1111/j.1600-6143.2004.00546.x

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

Cerulenin has been shown to reduce body weight and hepatic steatosis in murine models of obesity by inhibiting fatty acid synthase (FAS). We have shown that attenuating intrahepatocyte lipid content diminished the sensitivity of ob/ob mice to ischemia/reperfusion injury and improved survival after liver transplantation. The mechanism of action is by inhibition of fatty acid metabolism by downregulating PPARalpha, as well as mitochondrial uncoupling protein 2 (UCP2), with a concomitant increase in ATP. A short treatment course of cerulenin prior to I/R injury is ideal for protection of steatotic livers. Cerulenin opens the potential for expanding the use of steatotic livers in transplantation.

引用

页码：1440 / 1447

页数：8

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