Fatty Acid Synthase Blockade Protects Steatotic Livers from Warm Ischemia Reperfusion Injury and Transplantation
Year: 2004
Type: article
Abstract: 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.
Authors: Kenneth D. Chavin, Ryan N. Fiorini, Stephen Shafizadeh, Gang Cheng, Chidan Wan, Zachary Evans, David Rodwell, Carmen Polito, Julia K. Haines, G. Mark Baillie, Michael G. Schmidt
Institution: Medical University of South Carolina
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,300
OpenAlex ID: W1971723316