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Fatty Acid Synthase Blockade Protects Steatotic Livers from Warm Ischemia Reperfusion Injury and Transplantation
Author(s) -
Chavin Kenneth D.,
Fiorini Ryan N.,
Shafizadeh Stephen,
Cheng Gang,
Wan Chidan,
Evans Zachary,
Rodwell David,
Polito Carmen,
Haines Julia K.,
Baillie G. Mark,
Schmidt Michael G.
Publication year - 2004
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00546.x
Subject(s) - cerulenin , fatty acid synthase , steatosis , medicine , reperfusion injury , transplantation , lipogenesis , lipid metabolism , liver transplantation , fatty acid , beta oxidation , atp synthase , ischemia , fatty liver , fatty acid synthesis , endocrinology , pharmacology , metabolism , biochemistry , biology , enzyme , disease
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 PPARα, 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.